Aim: Preclinical evaluation of a cytotoxic copper (II) complex formulated in long circulating nanoliposomes for melanoma treatment. Materials & methods: Liposomal nanoformulations of the copper complex were characterized in terms of thermodynamic behavior (differential scanning calorimeter), pH-sensitivity (spectrophotometry) and antiproliferative effects against murine melanoma B16F10 cells in vitro. Preclinical studies were performed in a C57BL/6 syngeneic melanoma model. Results: Nanoformulations were thermodynamically stable, and CHEMS-containing nanoliposomes were pH-sensitive and preserved the antiproliferative properties of the copper compound. These nanoformulations significantly impaired tumor progression in vivo, devoid of toxic side effects, compared with control mice or mice treated with the free metallodrug. Conclusion: Copper complex-containing nanoliposomes demonstrate high anticancer efficacy and safety, constituting a step forward to the development of more effective therapeutic strategies against melanoma.