The effectiveness of immunotherapy in killing melanoma is hindered by a T-cell deficiency and the lack of tumor immunogenicity. Consequently, there is an urgent need for a platform that can further activate the immune system and boost the immune response of the host to tumors. Compared with monotherapy, combination therapy shows promise in improving treatment efficacy and response rates. This study introduces the pioneering use of a rationally designed active targeting nanoplatform to bind axitinib, paclitaxel, and verteporfin to human serum albumin (APV@HSA NPs). APV@HSA NPs have demonstrated the capability to induce dual-induced apoptosis in tumor cells through chemo- and photodynamic effects, while also enhancing immunogenic cell death and promoting dendritic cell maturation. Additionally, the platform promoted the production of CD8