Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 has emerged as a promising approach in lung cancer treatment, offering enhanced immune responses against cancer cells by acting at different stages of T cell activation. This therapy, which combines anti-PD-1/PD-L1 and anti-CTLA-4 agents, has shown potential to improve efficacy while increasing the risk of adverse reactions. Recent advancements in bispecific antibodies (BsAbs) have made this dual targeting more feasible, aiming to reduce toxicity without compromising efficacy. The review highlights the role of dual blockade immunotherapy in treating lung cancer, elucidates its preclinical mechanisms, and discusses current clinical trial advancements. It also provides insights into potential combinations with other strategies to optimize future treatment modes. Lung cancer remains a leading cause of cancer-related deaths, with advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) being the main subtypes. While chemotherapy has been the standard treatment, it often fails to halt disease progression. Immune checkpoint inhibitors (ICIs), particularly targeting PD-1/PD-L1 and CTLA-4, have significantly improved outcomes. However, about 20-30% of patients with advanced NSCLC receiving ICI monotherapy show limited efficacy. Combination immunotherapy, including dual ICI and BsAbs, has become a novel hotspot in lung cancer treatment. The Cancer-Immunity Cycle is crucial for effective immune-mediated destruction of cancer cells. PD-1/PD-L1 and CTLA-4 inhibitors play key roles in restoring immune activity. Dual blockade immunotherapy effectively overcomes immune tolerance, enabling bypass of resistance. The combination of PD-1/PD-L1 and CTLA-4 inhibitors significantly decreases the proportion of exhausted T cells while increasing active effector T cells, enhancing the immune response. BsAbs, which bind two different epitopes, offer an alternative approach to enhance immunity and reduce toxicity. They can target multiple immune inhibitory checkpoints, effectively bypassing the immune tolerance of the tumor microenvironment. Preclinical studies have shown that dual ICI combination therapy, such as nivolumab and ipilimumab, significantly improves survival and response rates in NSCLC and SCLC patients. Clinical trials, including CheckMate 012, CheckMate 568, and CheckMate 227, have demonstrated the efficacy and safety of dual ICI combination therapy in advanced NSCLC. The Phase III MYSTIC study showed that dual ICI combination therapy did not significantly improve survival compared to chemotherapy, but subgroup analysis identified TMB as a potential predictive biomarker. The ARCTIC study showed some numerical improvement in median OS with dual immunotherapy in patients with PD-L1 expression <25%. BsAbs such as Cadonilimab (AK104) and KN046 have shown promising efficacy and tolerability in clinical trials. CadDual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 has emerged as a promising approach in lung cancer treatment, offering enhanced immune responses against cancer cells by acting at different stages of T cell activation. This therapy, which combines anti-PD-1/PD-L1 and anti-CTLA-4 agents, has shown potential to improve efficacy while increasing the risk of adverse reactions. Recent advancements in bispecific antibodies (BsAbs) have made this dual targeting more feasible, aiming to reduce toxicity without compromising efficacy. The review highlights the role of dual blockade immunotherapy in treating lung cancer, elucidates its preclinical mechanisms, and discusses current clinical trial advancements. It also provides insights into potential combinations with other strategies to optimize future treatment modes. Lung cancer remains a leading cause of cancer-related deaths, with advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) being the main subtypes. While chemotherapy has been the standard treatment, it often fails to halt disease progression. Immune checkpoint inhibitors (ICIs), particularly targeting PD-1/PD-L1 and CTLA-4, have significantly improved outcomes. However, about 20-30% of patients with advanced NSCLC receiving ICI monotherapy show limited efficacy. Combination immunotherapy, including dual ICI and BsAbs, has become a novel hotspot in lung cancer treatment. The Cancer-Immunity Cycle is crucial for effective immune-mediated destruction of cancer cells. PD-1/PD-L1 and CTLA-4 inhibitors play key roles in restoring immune activity. Dual blockade immunotherapy effectively overcomes immune tolerance, enabling bypass of resistance. The combination of PD-1/PD-L1 and CTLA-4 inhibitors significantly decreases the proportion of exhausted T cells while increasing active effector T cells, enhancing the immune response. BsAbs, which bind two different epitopes, offer an alternative approach to enhance immunity and reduce toxicity. They can target multiple immune inhibitory checkpoints, effectively bypassing the immune tolerance of the tumor microenvironment. Preclinical studies have shown that dual ICI combination therapy, such as nivolumab and ipilimumab, significantly improves survival and response rates in NSCLC and SCLC patients. Clinical trials, including CheckMate 012, CheckMate 568, and CheckMate 227, have demonstrated the efficacy and safety of dual ICI combination therapy in advanced NSCLC. The Phase III MYSTIC study showed that dual ICI combination therapy did not significantly improve survival compared to chemotherapy, but subgroup analysis identified TMB as a potential predictive biomarker. The ARCTIC study showed some numerical improvement in median OS with dual immunotherapy in patients with PD-L1 expression <25%. BsAbs such as Cadonilimab (AK104) and KN046 have shown promising efficacy and tolerability in clinical trials. Cad