Abstract
Melanoma remains a major therapeutic challenge in dermatologic oncology because of its aggressive nature and high mortality rate, with traditional therapeutic approaches exhibiting significant limitations in efficacy. Although nanodrug delivery systems (NDS) present a promising paradigm to overcome existing therapeutic bottlenecks, a substantial translational gap persists between intricate preclinical material engineering and successful clinical translation. Notably, strategies designed to target the tumor microenvironment (TME) have shown promising progress in the clinical management of melanoma. This review contextualizes the latest breakthroughs in melanoma-targeted NDS, elucidating how advanced nanocarriers exploit physiological and metabolic imbalances within the TME to reverse local immunosuppression and actively remodel the antitumor niche. Building on this foundation, we critically evaluate the performance of major synthetic platforms, including lipidic, polymeric, and inorganic materials. We also assess emerging biological and biomimetic nanocarriers, specifically comparing their biocompatibility and drug-loading capacities. Furthermore, we summarize the current landscape of Phase I-III clinical trials of nanomedicine-based therapies for melanoma. This review proposes a translational framework for the rational development of next-generation melanoma nanotherapeutics.