This comprehensive review explores the intricate mechanisms of PANoptosis, a convergence of apoptosis, pyroptosis, and necroptosis, and its implications in cancer. PANoptosis plays a crucial role in cell death and immune response regulation, with significant impacts on various cancers, including respiratory, digestive, genitourinary, gliomas, and breast cancers. The review highlights the molecular pathways of each cell death mechanism and their crosstalk within PANoptosis, emphasizing shared components like caspases and the PANoptosome complex. It discusses the dynamic interplay between tumors and their microenvironments (TME), focusing on the roles of different immune cells and their interactions with cancer cells. The review also presents new breakthroughs in cancer therapy, emphasizing the potential of targeting PANoptosis to enhance anti-tumor immunity. Various strategies to manipulate PANoptosis pathways for therapeutic purposes are outlined, including targeting key signaling molecules like caspases, NLRP3, RIPK1, and RIPK3. The potential of novel treatments like immunogenic PANoptosis-initiated therapies and nanoparticle-based strategies is also explored.This comprehensive review explores the intricate mechanisms of PANoptosis, a convergence of apoptosis, pyroptosis, and necroptosis, and its implications in cancer. PANoptosis plays a crucial role in cell death and immune response regulation, with significant impacts on various cancers, including respiratory, digestive, genitourinary, gliomas, and breast cancers. The review highlights the molecular pathways of each cell death mechanism and their crosstalk within PANoptosis, emphasizing shared components like caspases and the PANoptosome complex. It discusses the dynamic interplay between tumors and their microenvironments (TME), focusing on the roles of different immune cells and their interactions with cancer cells. The review also presents new breakthroughs in cancer therapy, emphasizing the potential of targeting PANoptosis to enhance anti-tumor immunity. Various strategies to manipulate PANoptosis pathways for therapeutic purposes are outlined, including targeting key signaling molecules like caspases, NLRP3, RIPK1, and RIPK3. The potential of novel treatments like immunogenic PANoptosis-initiated therapies and nanoparticle-based strategies is also explored.