It has been more than a decade since anti-PD-1 and anti-CTLA-4 antibodies were first introduced for the treatment of unresectable melanoma. The advent of these immunotherapies has dramatically transformed the treatment landscape. In recent years, anti-PD-1 antibodies have become the cornerstone of melanoma therapy, and the development of new treatment regimens has advanced rapidly in both Eastern and Western countries. However, clinical practice has revealed lower response rates in East Asian melanoma patients compared to Caucasian populations. This discrepancy may be partially attributed to T cell immune exhaustion within the tumor microenvironment, although the detailed mechanisms remain unclear. Moreover, there is currently no established treatment for BRAF wild-type melanoma that is resistant to anti-PD-1 antibodies. This review discusses the currently available therapeutic strategies for advanced melanoma and addresses the aforementioned challenges, highlighting recent efforts in both Eastern and Western regions.