The article discusses the role of non-apoptotic regulated cell death (RCD) mechanisms—ferroptosis, pyroptosis, and necroptosis—in enhancing the efficacy of anti-PD-1/PD-L1 immunotherapy for cancer treatment. These RCD forms are triggered by immune checkpoint inhibitors (ICIs), particularly anti-PD-1 and anti-PD-L1, which activate CD8+ T cells and promote the release of cytokines that induce RCD. The combination of RCD inducers with ICIs significantly improves antitumor effects by modifying the tumor microenvironment (TME) and enhancing immune responses. Ferroptosis, characterized by iron-dependent lipid peroxidation, is induced by nanomaterials and can be enhanced by PD-1/PD-L1 inhibitors. It plays a critical role in tumor immunity by increasing tumor antigen presentation and activating T cells. Pyroptosis, an inflammatory form of cell death, is associated with the release of pro-inflammatory signals that promote immune cell infiltration and enhance the effectiveness of immunotherapy. Necroptosis, a regulated form of necrosis, can be induced by targeting specific signaling pathways and enhances antitumor immunity by activating CD8+ T cells and promoting immune memory. The article highlights the potential of combining RCD mechanisms with anti-PD-1/PD-L1 therapy to overcome resistance and improve cancer treatment outcomes. It emphasizes the importance of understanding the molecular mechanisms underlying these RCD forms and their interactions with immune checkpoints. The review also discusses ongoing clinical trials exploring the application of non-apoptotic cell death in cancer immunotherapy, suggesting that targeting these pathways could lead to more effective and personalized cancer treatments.The article discusses the role of non-apoptotic regulated cell death (RCD) mechanisms—ferroptosis, pyroptosis, and necroptosis—in enhancing the efficacy of anti-PD-1/PD-L1 immunotherapy for cancer treatment. These RCD forms are triggered by immune checkpoint inhibitors (ICIs), particularly anti-PD-1 and anti-PD-L1, which activate CD8+ T cells and promote the release of cytokines that induce RCD. The combination of RCD inducers with ICIs significantly improves antitumor effects by modifying the tumor microenvironment (TME) and enhancing immune responses. Ferroptosis, characterized by iron-dependent lipid peroxidation, is induced by nanomaterials and can be enhanced by PD-1/PD-L1 inhibitors. It plays a critical role in tumor immunity by increasing tumor antigen presentation and activating T cells. Pyroptosis, an inflammatory form of cell death, is associated with the release of pro-inflammatory signals that promote immune cell infiltration and enhance the effectiveness of immunotherapy. Necroptosis, a regulated form of necrosis, can be induced by targeting specific signaling pathways and enhances antitumor immunity by activating CD8+ T cells and promoting immune memory. The article highlights the potential of combining RCD mechanisms with anti-PD-1/PD-L1 therapy to overcome resistance and improve cancer treatment outcomes. It emphasizes the importance of understanding the molecular mechanisms underlying these RCD forms and their interactions with immune checkpoints. The review also discusses ongoing clinical trials exploring the application of non-apoptotic cell death in cancer immunotherapy, suggesting that targeting these pathways could lead to more effective and personalized cancer treatments.