This systematic review and meta-analysis evaluated and compared the efficacy and safety of PD-1 and CTLA-4 monotherapies against traditional systemic therapies, as well as the dual regimens PD-1 + CTLA-4 and PD-1 + LAG-3 against their respective monotherapies, in patients with advanced unresectable melanoma. This evidence concerns the gene CTLA4 and melanoma.