Malignant melanoma frequently develops resistance to targeted agents and immune checkpoint blockade. The core reason lies in the impaired ability of malignant cells to undergo regulated cell death， along with the dominance of an immunosuppressive microenvironment， which limits the efficacy of solely targeting mitochondrial apoptosis. PANapoptosis integrates pyroptosis， apoptosis， and necroptosis， thereby enhancing tumor cell clearance， promoting the release of adenosine triphosphate （ATP） and antigens， and amplifying inflammatory and interferon signaling. These effects improve antigen presentation and effector immune cell recruitment， ultimately enhancing responses to immunotherapy. However， factors such as hypoxia， acidic environment， enhanced autophagy， and epigenetic silencing can hinder the initiation and amplification of PANapoptosis. This review summarizes the molecular architecture of PANapoptosis and its impact on the immune microenvironment of melanoma， as well as relevant resistance mechanisms, proposes that B-cell lymphoma 2-related protein A1 （BCL2A1） may play a negative regulatory role by inhibiting the PANapoptotic complex， and explores the potential of combining BCL2A1 targeting with PANapoptosis inducers as a direction for overcoming therapeutic resistance in melanoma.