• Participants must have a confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma or Stage III or IV NSCLC.

• Participants who have received the following previous therapy:

∙ Cohort 1 (Melanoma): Participants who have progressed within 12 weeks of last dose of anti-PD-1/PD-L1 blocking antibody and received BRAF/MEK inhibitor in those with BRAF mutations.

‣ Cohort 2 (NSCLC): Participants who should have received no more than 3 prior lines of therapy and:

⁃ those without oncogene-driven tumors: Have progressed within 12 weeks after last dose of anti-PD-1/PD-L1 blocking antibody

• those with oncogene-driven tumors: Have progressed during/after ≥1 targeted therapy AND either:

∙ platinum doublet chemotherapy

‣ Or within 12 weeks after last dose of anti-PD-1/PD-L1 blocking antibody

• Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Participants who is assessed as having at least one resectable lesion.

• Participants who have at least one measurable lesion, following resection of the lesion for IOV-4001 generation.

• Participants who have adequate organ function.

• Cardiac function test required.

• Pulmonary function test may be required.

• Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and up to 12 months.

⁃ Participants who are \>70 years of age may be allowed to enroll after the investigator discusses with the medical monitor.