Abstract： Melanoma originates from epidermal melanocytes and is the most malignant form of skin cancer, with an increasing incidence worldwide. In addition to the known pathological mutations in melanoma, the remodeling of epigenetic modification has recently been documented to orchestrate the malignant behaviors of tumor cells and anti-tumor immunity, emerging as an irreversible tumorigenic event that is more preventable and treatable with medications. As a hallmark characteristic of cancer, the disorder of cellular metabolism is also greatly implicated in tumor carcinogenesis and development. Accumulating evidence has revealed the close linkage between metabolism and epigenetics in multiple biological activities. In the pathogenesis of melanoma, the findings of other groups and our laboratory highlight the pivotal role of autophagy, mitochondrial function, and the oncometabolite acetyl-CoA, as well as their epigenetic modification. Targeted metabolism-associated epigenetic modulation might be a novel approach for melanoma therapy in the future.