<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Toppan Merrill Bridge  10.2.0.4 -->
<!--Based on XBRL 2.1-->
<!--Created on: 3/2/2023 8:38:22 PM-->
<!--Modified on: 3/2/2023 8:38:22 PM-->
<xsd:schema targetNamespace="http://www.nextcure.com/20221231" attributeFormDefault="unqualified" elementFormDefault="qualified" xmlns:xsd="http://www.w3.org/2001/XMLSchema" xmlns:ref="http://www.xbrl.org/2006/ref" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:xl="http://www.xbrl.org/2003/XLink" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:net="http://www.xbrl.org/2009/role/net" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:attributeFormDefault="unqualified" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:country="http://xbrl.sec.gov/country/2022" xmlns:currency="http://xbrl.sec.gov/currency/2022" xmlns:us-gaap="http://fasb.org/us-gaap/2022" xmlns:us-types="http://fasb.org/us-types/2022" xmlns:stpr="http://xbrl.sec.gov/stpr/2022" xmlns:us-roles="http://fasb.org/us-roles/2022" xmlns:negated="http://www.xbrl.org/2009/role/negated" xmlns:srt-types="http://fasb.org/srt-types/2022" xmlns:nxtc="http://www.nextcure.com/20221231" xmlns:enum2="http://xbrl.org/2020/extensible-enumerations-2.0" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:sic="http://xbrl.sec.gov/sic/2022" xmlns:srt-roles="http://fasb.org/srt-roles/2022" xmlns:utr="http://www.xbrl.org/2009/utr" xmlns:exch="http://xbrl.sec.gov/exch/2022" xmlns:naics="http://xbrl.sec.gov/naics/2022" xmlns:srt="http://fasb.org/srt/2022" xmlns:deprecated="http://www.xbrl.org/2009/role/deprecated" xmlns:dei="http://xbrl.sec.gov/dei/2022" xmlns:dtr="http://www.xbrl.org/2009/dtr" xmlns:cef="http://xbrl.sec.gov/cef/2022" xmlns:xbrldi="http://xbrl.org/2006/xbrldi">
  <xsd:annotation>
    <xsd:appinfo>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureStandardAndCustomAxisDomainDefaults" id="DisclosureStandardAndCustomAxisDomainDefaults">
        <link:definition>99900 - Disclosure - Standard And Custom Axis Domain Defaults</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/StatementBalanceSheets" id="StatementBalanceSheets">
        <link:definition>00100 - Statement - BALANCE SHEETS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/StatementStatementsOfOperationsAndComprehensiveLoss" id="StatementStatementsOfOperationsAndComprehensiveLoss">
        <link:definition>00200 - Statement - STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/StatementStatementsOfCashFlows" id="StatementStatementsOfCashFlows">
        <link:definition>00400 - Statement - STATEMENTS OF CASH FLOWS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureSummaryOfSignificantAccountingPoliciesRestrictedCashDetails" id="DisclosureSummaryOfSignificantAccountingPoliciesRestrictedCashDetails">
        <link:definition>40201 - Disclosure - Summary of Significant Accounting Policies - Restricted Cash (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureMarketableSecuritiesDetails" id="DisclosureMarketableSecuritiesDetails">
        <link:definition>40301 - Disclosure - Marketable Securities - (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureFairValueMeasurementsDetails" id="DisclosureFairValueMeasurementsDetails">
        <link:definition>40401 - Disclosure - Fair Value Measurements - (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosurePropertyAndEquipmentNetDetails" id="DisclosurePropertyAndEquipmentNetDetails">
        <link:definition>40501 - Disclosure - Property and Equipment, Net - (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureAccruedLiabilitiesAndOtherLiabilitiesDetails" id="DisclosureAccruedLiabilitiesAndOtherLiabilitiesDetails">
        <link:definition>40601 - Disclosure - Accrued Liabilities and Other Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureLeasesMaturitiesCalc2Details" id="DisclosureLeasesMaturitiesCalc2Details">
        <link:definition>40702 - Disclosure - Leases - Maturities (Calc 2) (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureLeasesMaturitiesDetails" id="DisclosureLeasesMaturitiesDetails">
        <link:definition>40702 - Disclosure - Leases - Maturities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureIncomeTaxesReconciliationDetails" id="DisclosureIncomeTaxesReconciliationDetails">
        <link:definition>41401 - Disclosure - Income Taxes - Reconciliation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureIncomeTaxesDeferredTaxAssetsDetails" id="DisclosureIncomeTaxesDeferredTaxAssetsDetails">
        <link:definition>41402 - Disclosure - Income Taxes - Deferred tax assets (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DocumentDocumentAndEntityInformation" id="DocumentDocumentAndEntityInformation">
        <link:definition>00090 - Document - Document and Entity Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/StatementBalanceSheetsParenthetical" id="StatementBalanceSheetsParenthetical">
        <link:definition>00105 - Statement - BALANCE SHEETS - (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/StatementStatementsOfStockholdersEquity" id="StatementStatementsOfStockholdersEquity">
        <link:definition>00300 - Statement - STATEMENTS OF STOCKHOLDERS EQUITY</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/StatementStatementsOfStockholdersEquityParenthetical" id="StatementStatementsOfStockholdersEquityParenthetical">
        <link:definition>00305 - Statement - STATEMENTS OF STOCKHOLDERS EQUITY (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureMarketableSecurities" id="DisclosureMarketableSecurities">
        <link:definition>10301 - Disclosure - Marketable Securities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureTermLoan" id="DisclosureTermLoan">
        <link:definition>10901 - Disclosure - Term Loan</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosurePreferredStock" id="DisclosurePreferredStock">
        <link:definition>11001 - Disclosure - Preferred Stock</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureCommonStock" id="DisclosureCommonStock">
        <link:definition>11101 - Disclosure - Common Stock</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureStockBasedCompensation" id="DisclosureStockBasedCompensation">
        <link:definition>11201 - Disclosure - Stock-Based Compensation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureNetLossPerShareAttributableToCommonStockholders" id="DisclosureNetLossPerShareAttributableToCommonStockholders">
        <link:definition>11301 - Disclosure - Net Loss per Share Attributable to Common Stockholders</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureIncomeTaxes" id="DisclosureIncomeTaxes">
        <link:definition>11401 - Disclosure - Income Taxes</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureEmployeeBenefitPlan" id="DisclosureEmployeeBenefitPlan">
        <link:definition>11501 - Disclosure - Employee Benefit Plan</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureMarketableSecuritiesTables" id="DisclosureMarketableSecuritiesTables">
        <link:definition>30303 - Disclosure - Marketable Securities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureStockBasedCompensationTables" id="DisclosureStockBasedCompensationTables">
        <link:definition>31203 - Disclosure - Stock-Based Compensation (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureNetLossPerShareAttributableToCommonStockholdersTables" id="DisclosureNetLossPerShareAttributableToCommonStockholdersTables">
        <link:definition>31303 - Disclosure - Net Loss per Share Attributable to Common Stockholders (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureIncomeTaxesTables" id="DisclosureIncomeTaxesTables">
        <link:definition>31403 - Disclosure - Income Taxes (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureNatureOfBusinessAndBasisOfPresentationPublicOfferingsAndCommonStockDetails" id="DisclosureNatureOfBusinessAndBasisOfPresentationPublicOfferingsAndCommonStockDetails">
        <link:definition>40101 - Disclosure - Nature of the Business and Basis of Presentation - Public Offerings and Common Stock (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureNatureOfBusinessAndBasisOfPresentationLiquidityDetails" id="DisclosureNatureOfBusinessAndBasisOfPresentationLiquidityDetails">
        <link:definition>40102 - Disclosure - Nature of the Business and Basis of Presentation - Liquidity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureSummaryOfSignificantAccountingPoliciesPropertyAndEquipmentAndLeasesDetails" id="DisclosureSummaryOfSignificantAccountingPoliciesPropertyAndEquipmentAndLeasesDetails">
        <link:definition>40202 - Disclosure - Summary of Significant Accounting Policies - Property and Equipment and Leases (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureTermLoanOtherDetails" id="DisclosureTermLoanOtherDetails">
        <link:definition>40901 - Disclosure - Term Loan - Other (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosurePreferredStockDetails" id="DisclosurePreferredStockDetails">
        <link:definition>41001 - Disclosure - Preferred Stock (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureCommonStockDetails" id="DisclosureCommonStockDetails">
        <link:definition>41101 - Disclosure - Common Stock (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureStockBasedCompensationStockOptionsDetails" id="DisclosureStockBasedCompensationStockOptionsDetails">
        <link:definition>41201 - Disclosure - Stock-Based Compensation - Stock options (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureStockBasedCompensationStockBasedCompensationExpenseDetails" id="DisclosureStockBasedCompensationStockBasedCompensationExpenseDetails">
        <link:definition>41202 - Disclosure - Stock-Based Compensation - Stock based compensation expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureStockBasedCompensationAssumptionsDetails" id="DisclosureStockBasedCompensationAssumptionsDetails">
        <link:definition>41203 - Disclosure - Stock-Based Compensation - Assumptions (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureStockBasedCompensationRestrictedCommonStockDetails" id="DisclosureStockBasedCompensationRestrictedCommonStockDetails">
        <link:definition>41204 - Disclosure - Stock-Based Compensation - Restricted Common Stock (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureNetLossPerShareAttributableToCommonStockholdersAntiDilutiveEffectDetails" id="DisclosureNetLossPerShareAttributableToCommonStockholdersAntiDilutiveEffectDetails">
        <link:definition>41301 - Disclosure - Net Loss per Share Attributable to Common Stockholders - Anti-dilutive effect (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureEmployeeBenefitPlanDetails" id="DisclosureEmployeeBenefitPlanDetails">
        <link:definition>41501 - Disclosure - Employee Benefit Plan (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureNatureOfBusinessAndBasisOfPresentation" id="DisclosureNatureOfBusinessAndBasisOfPresentation">
        <link:definition>10101 - Disclosure - Nature of the Business and Basis of Presentation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureSummaryOfSignificantAccountingPolicies" id="DisclosureSummaryOfSignificantAccountingPolicies">
        <link:definition>10201 - Disclosure - Summary of Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureFairValueMeasurements" id="DisclosureFairValueMeasurements">
        <link:definition>10401 - Disclosure - Fair Value Measurements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosurePropertyAndEquipmentNet" id="DisclosurePropertyAndEquipmentNet">
        <link:definition>10501 - Disclosure - Property and Equipment, Net</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureAccruedLiabilitiesAndOtherLiabilities" id="DisclosureAccruedLiabilitiesAndOtherLiabilities">
        <link:definition>10601 - Disclosure - Accrued Liabilities and Other Liabilities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureLeases" id="DisclosureLeases">
        <link:definition>10701 - Disclosure - Leases</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureCommitmentsAndContingencies" id="DisclosureCommitmentsAndContingencies">
        <link:definition>10801 - Disclosure - Commitments and Contingencies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureSummaryOfSignificantAccountingPoliciesPolicies" id="DisclosureSummaryOfSignificantAccountingPoliciesPolicies">
        <link:definition>20202 - Disclosure - Summary of Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureSummaryOfSignificantAccountingPoliciesTables" id="DisclosureSummaryOfSignificantAccountingPoliciesTables">
        <link:definition>30203 - Disclosure - Summary of Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureFairValueMeasurementsTables" id="DisclosureFairValueMeasurementsTables">
        <link:definition>30403 - Disclosure - Fair Value Measurements (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosurePropertyAndEquipmentNetTables" id="DisclosurePropertyAndEquipmentNetTables">
        <link:definition>30503 - Disclosure - Property and Equipment, Net (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureAccruedLiabilitiesAndOtherLiabilitiesTables" id="DisclosureAccruedLiabilitiesAndOtherLiabilitiesTables">
        <link:definition>30603 - Disclosure - Accrued Liabilities and Other Liabilities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureLeasesTables" id="DisclosureLeasesTables">
        <link:definition>30703 - Disclosure - Leases (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureSummaryOfSignificantAccountingPoliciesAdditionalInformationDetails" id="DisclosureSummaryOfSignificantAccountingPoliciesAdditionalInformationDetails">
        <link:definition>40203 - Disclosure - Summary of Significant Accounting Policies - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.nextcure.com/role/DisclosureLeasesOtherInformationDetails" id="DisclosureLeasesOtherInformationDetails">
        <link:definition>40701 - Disclosure - Leases - Other Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:linkbaseRef xlink:type="simple" xlink:href="nxtc-20221231_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:linkbaseRef xlink:type="simple" xlink:href="nxtc-20221231_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:linkbaseRef xlink:type="simple" xlink:href="nxtc-20221231_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:linkbaseRef xlink:type="simple" xlink:href="nxtc-20221231_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:title="Calculation Links, all" />
    </xsd:appinfo>
  </xsd:annotation>
  <xsd:import namespace="http://xbrl.sec.gov/dei/2022" schemaLocation="https://xbrl.sec.gov/dei/2022/dei-2022.xsd" />
  <xsd:import namespace="http://fasb.org/us-roles/2022" schemaLocation="https://xbrl.fasb.org/us-gaap/2022/elts/us-roles-2022.xsd" />
  <xsd:import namespace="http://www.xbrl.org/2009/role/negated" schemaLocation="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd" />
  <xsd:import namespace="http://www.xbrl.org/dtr/type/2020-01-21" schemaLocation="https://www.xbrl.org/dtr/type/2020-01-21/types.xsd" />
  <xsd:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd" />
  <xsd:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd" />
  <xsd:import namespace="http://fasb.org/us-gaap/2022" schemaLocation="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd" />
  <xsd:import namespace="http://fasb.org/srt/2022" schemaLocation="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd" />
  <xsd:element id="nxtc_PropertyPlantAndEquipmentEstimatedUsefulLivesTableTextBlock" name="PropertyPlantAndEquipmentEstimatedUsefulLivesTableTextBlock" nillable="true" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <xsd:element id="nxtc_ResearchEquipmentMember" name="ResearchEquipmentMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element id="nxtc_AccruedClinicalTrialCostsCurrent" name="AccruedClinicalTrialCostsCurrent" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <xsd:element id="nxtc_AccruedOperatingExpensesCurrent" name="AccruedOperatingExpensesCurrent" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <xsd:element id="nxtc_CommonStockTextBlock" name="CommonStockTextBlock" nillable="true" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <xsd:element id="nxtc_NumberOfVotesPerShare" name="NumberOfVotesPerShare" nillable="true" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <xsd:element id="nxtc_A2015OmnibusIncentivePlanMember" name="A2015OmnibusIncentivePlanMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element id="nxtc_DeferredTaxLiabilitiesDepreciationAndAmortization" name="DeferredTaxLiabilitiesDepreciationAndAmortization" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <xsd:element id="nxtc_DeferredTaxAssetsTaxCreditCarryforwardsResearchAndDevelopmentFederal" name="DeferredTaxAssetsTaxCreditCarryforwardsResearchAndDevelopmentFederal" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="nxtc_DeferredTaxAssetsTaxCreditCarryforwardsResearchAndDevelopmentState" name="DeferredTaxAssetsTaxCreditCarryforwardsResearchAndDevelopmentState" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="nxtc_PaymentsOfUnderwritingDiscountsAndCommissions" name="PaymentsOfUnderwritingDiscountsAndCommissions" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="credit" />
  <xsd:element id="nxtc_OmnibusIncentive2019PlanMember" name="OmnibusIncentive2019PlanMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element id="nxtc_EmployeeStockPurchase2019PlanMember" name="EmployeeStockPurchase2019PlanMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element id="nxtc_ShareBasedCompensationArrangementIncreaseInSharesForIssuanceAsPercentageOfNumberOfCommonStockOutstanding" name="ShareBasedCompensationArrangementIncreaseInSharesForIssuanceAsPercentageOfNumberOfCommonStockOutstanding" nillable="true" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <xsd:element id="nxtc_ShareBasedCompensationArrangementThresholdNumberOfCommonStockForIssuanceUnderPlan" name="ShareBasedCompensationArrangementThresholdNumberOfCommonStockForIssuanceUnderPlan" nillable="true" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <xsd:element id="nxtc_RequiredReserveRestrictedCashCurrent" name="RequiredReserveRestrictedCashCurrent" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="nxtc_PreferredStockAbstract" name="PreferredStockAbstract" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element id="nxtc_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardExpirationPeriod" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardExpirationPeriod" nillable="true" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <xsd:element id="nxtc_OmnibusIncentive2015PlanAndEmployeeStockPurchase2019PlanMember" name="OmnibusIncentive2015PlanAndEmployeeStockPurchase2019PlanMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element id="nxtc_MarketableSecuritiesAndCashEquivalents" name="MarketableSecuritiesAndCashEquivalents" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="nxtc_ScheduleOfAvailableForSaleSecuritiesMaturitiesTableTextBlock" name="ScheduleOfAvailableForSaleSecuritiesMaturitiesTableTextBlock" nillable="true" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <xsd:element id="nxtc_InterestIncomeNonOperating" name="InterestIncomeNonOperating" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="credit" />
  <xsd:element id="nxtc_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAndOther" name="DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAndOther" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="nxtc_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTaxAdjusted" name="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTaxAdjusted" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="credit" />
  <xsd:element id="nxtc_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsAmortizedCost" name="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsAmortizedCost" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="nxtc_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsFairValue" name="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsFairValue" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element name="AccruedSponsoredResearchExpenseCurrent" id="nxtc_AccruedSponsoredResearchExpenseCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="DepreciationDepletionAndAmortizationAndOther" id="nxtc_DepreciationDepletionAndAmortizationAndOther" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
  <xsd:element name="EarningsPerSharesBasicAndDilutedAbstract" id="nxtc_EarningsPerSharesBasicAndDilutedAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="FairValuesAssetsLevel1ToLevel2TransfersAmount" id="nxtc_FairValuesAssetsLevel1ToLevel2TransfersAmount" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="FairValuesAssetsLevel2ToLevel1TransfersAmount" id="nxtc_FairValuesAssetsLevel2ToLevel1TransfersAmount" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="EarningsPerSharesBasicAndDilutedOtherDisclosuresAbstract" id="nxtc_EarningsPerSharesBasicAndDilutedOtherDisclosuresAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="NoncashOperatingLeaseExpense" id="nxtc_NoncashOperatingLeaseExpense" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
  <xsd:element name="OperatingLeaseLiabilitiesInitialLeaseRecognitionAmount" id="nxtc_OperatingLeaseLiabilitiesInitialLeaseRecognitionAmount" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="AccruedAndOtherLiabilitiesCurrent" id="nxtc_AccruedAndOtherLiabilitiesCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="IncreaseDecreaseInAccruedAndOtherCurrentLiabilities" id="nxtc_IncreaseDecreaseInAccruedAndOtherCurrentLiabilities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="DeferredTaxAssetsOperatingLeaseLiabilities" id="nxtc_DeferredTaxAssetsOperatingLeaseLiabilities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="debit" />
  <xsd:element name="DeferredTaxAssetsCapitalizedResearchAndDevelopment" id="nxtc_DeferredTaxAssetsCapitalizedResearchAndDevelopment" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="debit" />
</xsd:schema>
