Abstract: Melanoma is a highly malignant and metastatic skin tumor, with traditional treatment methods showing limited efficacy. This highlights the urgent need for novel, effective, and safe therapeutic strategies. Arsenic compounds, derived from traditional Chinese medicine, offer anti-tumor advantages through multiple pathways and targets. This review explores the mechanisms by which arsenic compounds act in melanoma, primarily including the induction of apoptosis and ferroptosis, regulation of tumor cell autophagy, and inhibition of angiogenesis, all of which demonstrate significant anti-melanoma potential. However, the rapid renal clearance and inherent toxicity of arsenic compounds pose challenges for their clinical application. The development of nanoparticle drug delivery systems has partially addressed these challenges, improving the therapeutic efficacy of arsenic compounds in melanoma treatment while reducing systemic toxicity.