PANoptosis is a convergence of apoptosis, pyroptosis, and necroptosis, playing a crucial role in cell death and immune response regulation. This review explores the molecular mechanisms of PANoptosis and its implications in cancer. PANoptosis involves shared components like caspases and the PANoptosome complex, and it plays a significant role in various cancers, including respiratory, digestive, genitourinary, gliomas, and breast cancers. The study highlights the interwoven relationship between PANoptosis and the tumor microenvironment (TME), illustrating how PANoptosis influences immune cell behavior and tumor progression. It emphasizes the dynamic interplay between tumors and their microenvironments, focusing on the roles of different immune cells and their interactions with cancer cells. The review presents new breakthroughs in cancer therapy, emphasizing the potential of targeting PANoptosis to enhance anti-tumor immunity. It outlines various strategies to manipulate PANoptosis pathways for therapeutic purposes, such as 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. PANoptosis is associated with cancer progression and treatment, and its role in the tumor microenvironment is crucial for understanding cancer biology and developing new therapeutic strategies. The review discusses the mechanisms and crosstalk events in PANoptosis, the association of PANoptosis with cancer, and the potential of targeting PANoptosis for cancer therapy. The study also highlights the importance of understanding the interaction between PANoptosis and the TME in cancer treatment. The review concludes that targeting PANoptosis could be a promising strategy for cancer therapy, as it can enhance anti-tumor immunity and provide a feasible approach to improve the efficacy of cancer immunotherapy.PANoptosis is a convergence of apoptosis, pyroptosis, and necroptosis, playing a crucial role in cell death and immune response regulation. This review explores the molecular mechanisms of PANoptosis and its implications in cancer. PANoptosis involves shared components like caspases and the PANoptosome complex, and it plays a significant role in various cancers, including respiratory, digestive, genitourinary, gliomas, and breast cancers. The study highlights the interwoven relationship between PANoptosis and the tumor microenvironment (TME), illustrating how PANoptosis influences immune cell behavior and tumor progression. It emphasizes the dynamic interplay between tumors and their microenvironments, focusing on the roles of different immune cells and their interactions with cancer cells. The review presents new breakthroughs in cancer therapy, emphasizing the potential of targeting PANoptosis to enhance anti-tumor immunity. It outlines various strategies to manipulate PANoptosis pathways for therapeutic purposes, such as 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. PANoptosis is associated with cancer progression and treatment, and its role in the tumor microenvironment is crucial for understanding cancer biology and developing new therapeutic strategies. The review discusses the mechanisms and crosstalk events in PANoptosis, the association of PANoptosis with cancer, and the potential of targeting PANoptosis for cancer therapy. The study also highlights the importance of understanding the interaction between PANoptosis and the TME in cancer treatment. The review concludes that targeting PANoptosis could be a promising strategy for cancer therapy, as it can enhance anti-tumor immunity and provide a feasible approach to improve the efficacy of cancer immunotherapy.