Melanoma is characterized by its aggressiveness, high metastatic potential, and numerous mutations, which limit the effectiveness of current treatments. To address this issue, we developed a dissolvable microneedle (MN) system composed of poly(2-ethyl-2-oxazoline) (PEtOz) and chondroitin sulfate (CS). This MN system was loaded with liposomes containing both a NIR-II photothermal small molecule (IRLy) and the natural anticancer agent Gambogic acid (GA), forming Lip(IRLy + GA) MNs. The integration of the dissolvable microneedle with drug-loaded liposomes aligns with the mechanical properties and skin penetration efficiency required for effective drug delivery. It enables minimally invasive, painless, and precise administration of IRLy and GA. Under NIR-II 1064 nm laser irradiation, Lip(IRLy + GA) effectively inhibited melanoma by disrupting blood vessels, inducing apoptosis, and altering mitochondrial membrane potential. In a subcutaneous melanoma (A375) model in nude mice, the combination of Lip(IRLy + GA) and laser treatment demonstrated a synergistic effect, enhancing both photothermal and chemotherapeutic outcomes. This research presents a promising strategy that combines NIR-II photothermal agents with natural chemotherapeutic drugs and highlights the potential of microneedles in combination therapies for superficial skin cancers like melanoma.