<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0609</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2026-06-05</periodOfReport>

    <issuer>
        <issuerCik>0001819133</issuerCik>
        <issuerName>Tango Therapeutics, Inc.</issuerName>
        <issuerTradingSymbol>TNGX</issuerTradingSymbol>
        <issuerForeignTradingSymbol></issuerForeignTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001730866</rptOwnerCik>
            <rptOwnerName>Calhoun Lesley Ann</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerNonUSAddressFlag>false</rptOwnerNonUSAddressFlag>
            <rptOwnerStreet1>C/O TANGO THERAPEUTICS, INC.,</rptOwnerStreet1>
            <rptOwnerStreet2>201 BROOKLINE AVE., SUITE 901</rptOwnerStreet2>
            <rptOwnerCity>BOSTON</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02215</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>true</isDirector>
            <isOfficer>false</isOfficer>
            <isTenPercentOwner>false</isTenPercentOwner>
            <isOther>false</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <aff10b5One>false</aff10b5One>

    <nonDerivativeTable>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2026-06-05</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>A</transactionCode>
                <equitySwapInvolved>false</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>4000</value>
                    <footnoteId id="F1"/>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>16500</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
    </nonDerivativeTable>

    <derivativeTable>
        <derivativeTransaction>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>20.22</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2026-06-05</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>A</transactionCode>
                <equitySwapInvolved>false</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>25000</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <value>2036-06-05</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>25000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>25000</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeTransaction>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">These shares are represented by restricted stock units (the &quot;RSUs&quot;). Each RSU represents a contingent right to receive one share of Common Stock of the Issuer. The RSUs will vest in their entirety on the earlier of: (i) June 5, 2027 and (ii) the date of the next annual meeting of stockholders, in each case subject to the Reporting Person's continuous service with the Issuer as of each such vesting date.</footnote>
        <footnote id="F2">This option shall vest and become exercisable in 12 substantially equal monthly installments over a period of one year, with the first vesting date on July 5, 2026, subject to the Reporting Person's continuous service with the Issuer as of each such vesting date.</footnote>
    </footnotes>

    <remarks>Exhibit 24: Power of Attorney</remarks>

    <ownerSignature>
        <signatureName>/s/ Julie Fogarty, as attorney-in-fact</signatureName>
        <signatureDate>2026-06-08</signatureDate>
    </ownerSignature>
</ownershipDocument>
