Inclusion Criteria:
* Males and females age ≥ 18 years Enrollment of patients ≥ 70 years of age may be allowed at principal investigator discretion.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
* At least one measurable target lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
* Lesions in previously irradiated areas (or other local therapy) should not be selected as target lesions, unless treatment was ≥ 3 months prior to Screening, and there has been demonstrated disease progression in that lesion
* Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to initiating treatment
* Patients with unresectable or metastatic melanoma (stage IIIc or stage IV)
* Patients must have progressed following 1-3 prior systemic therapy including a programmed cell death protein-1 (PD-1) blocking antibody; and if proto-oncogene B-Raf (BRAF) V600 mutation positive, a BRAF inhibitor or BRAF inhibitor in combination mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor
* At least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm in diameter post-resection to generate TIL; surgical removal with minimal morbidity (defined as any procedure for which expected hospitalization is ≤ 3 days)
* Adequate hematologic and organ function
* Patients must have recovered from all prior therapy-related adverse events (AEs) to ≤ grade 1 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0), except for alopecia or vitiligo, prior to enrollment (tumor resection)
* Patients with documented ≥ grade 2 diarrhea or colitis because of previous treatment with immune checkpoint inhibitor(s) must have been asymptomatic for at least 6 months and/or had a normal colonoscopy post-immune checkpoint inhibitor treatment, by visual assessment, prior to tumor resection
* Patients with immunotherapy-related endocrinopathies stable for at least 6 weeks (eg, hypothyroidism), and controlled with hormonal replacement (non-corticosteroids), are allowed
* Patients must have a washout period of ≥ 28 days from prior anticancer therapy(ies) to the start of the planned reduced dose lymphodepletion (RDL) preconditioning regimen:
* Targeted therapy: MEK/BRAF or other targeted agents
* Chemotherapy
* Immunotherapy: anti-CTLA-4/anti-PD-1, other monoclonal antibodies (mAb), or vaccine
* Palliative radiation therapy is permitted so long as it does not involve lesions being selected for TIL, or as target or non-target lesions. Washout is not required if all related toxicities have resolved to ≤ grade 1 as per CTCAE v 5.0
* Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and for 12 months following the last dose of IL-2 or until the first dose of the next anti-cancer therapy, whichever occurs first
Exclusion Criteria:
* Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study
* Is pregnant or breastfeeding
* Patients who have active medical illness(es) that would pose increased risk for study participation, including active systemic infections requiring systemic antibiotics, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system
* Patients who have been shown to be BRAF mutation positive (V600), but have not received prior systemic therapy with a BRAF inhibitor alone or a BRAF inhibitor in combination with a MEK inhibitor
* Patients who have received an organ allograft or prior cell transfer therapy
* Patients with melanoma of uveal/ocular origin
* Patients who have a history of hypersensitivity to any component or excipient of Lifileucel or other study drugs
* Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency disease \[SCID\] and acquired immunodeficiency syndrome \[AIDS\])
* Patients who have a left ventricular ejection fraction (LVEF) \< 45% or New York Heart Association (NYHA) functional classification class \> 1
* Patients who have a documented forced expiratory volume in 1 second (FEV1) of ≤ 60%
* Patients who have had another primary malignancy within the previous 3 years (except for carcinoma in situ of the breast, cervix, or bladder; localized prostate cancer; and non-melanoma skin cancer that has been adequately treated)
* Patients with symptomatic and/or untreated brain metastases (of any size and any number)
* Other protocol defined inclusion/exclusion criteria could apply
