Inclusion Criteria:

• Participant must be ≥ 16 years of age at the time of signing the informed consent and assent.
• Participants who are > 70 years of age may be allowed to enroll after the investigator discusses with the medical monitor.
• Participant must have a confirmed diagnosis of histologically confirmed unresectable or metastatic UPS (Cohort 1) or DDLPS (Cohort 2), with or without a well-differentiated component, who have received ≥ 1 and a maximum of 3 prior systemic therapies, including ≥ 1 anthracycline-based regimen.
• Participant has demonstrated progressive disease on or after the last line of therapy.
• Participant is assessed as having at least one resectable lesion (or aggregate lesions) with an estimated minimum diameter of 1.5 cm (short axis) for lifileucel generation.
• Following tumor resection for lifileucel generation, the participant will have at least one measurable lesion, as defined by RECIST v1.1 at Baseline.
• Participant is expected to achieve washout from investigational or anticancer therapy(ies).
• If the participant has preplanned surgical procedure(s), the procedure will take place at least 14 days (for major operative procedures) prior to the tumor resection. Wound healing will have occurred, and all complications will have resolved at the time of tumor resection.
• Participant has recovered from all prior anticancer treatment-related AEs to Grade ≤ 1(per NCI-CTCAE), except for peripheral neuropathy, alopecia, or vitiligo.
• Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control.
• Participants must have adequate organ function.
• Participant is willing to receive optimal supportive care, including intensive care, from enrollment until the first post-treatment tumor assessment.

Exclusion Criteria:

• Participant has symptomatic untreated brain metastases.
• The participant has an ECOG performance status of ≥ 2, a need for urgent therapy due to rapidly progressive disease or tumor mass effect, or an estimated life expectancy of< 6 months.
• Participant has an active medical illness(es) that, in the opinion of the investigator, would pose increased risks for study participation.
• Participant has any form of primary immunodeficiency (eg, severe combined immunodeficiency disease [SCID] or AIDS).
• Participant has a history of hypersensitivity to any component of the study intervention.
• Participant had another primary malignancy within the previous 3 years (except for those that do not require treatment or have been curatively treated > 1 year ago, and in the judgment of the investigator does not pose a significant risk of recurrence.

Other protocol defined inclusion/exclusion criteria could apply.