This study presents a novel nanoplatform, ICG@MnO₂@Exo-anti-PD-L1, for combined photodynamic therapy (PDT) and immunotherapy against non-small cell lung cancer (NSCLC). The platform consists of indocyanine green (ICG), a photosensitizer, encapsulated in hollow manganese dioxide (MnO₂) nanospheres, which are then enclosed in reprogrammed exosomes modified with anti-PD-L1 monoclonal antibodies. This design enables targeted delivery to PD-L1-expressing cancer cells, where the MnO₂ catalyzes the conversion of hydrogen peroxide (H₂O₂) to oxygen, alleviating tumor hypoxia. ICG generates singlet oxygen under near-infrared (NIR) irradiation, leading to tumor cell death. Additionally, MnO₂ is reduced to Mn²⁺, which polarizes macrophages from M2 to M1, enhancing T cell activation and immune response. The system effectively modulates the tumor microenvironment (TME), improving PDT efficiency and immunotherapy outcomes. In vitro and in vivo experiments demonstrated that ICG@MnO₂@Exo-anti-PD-L1 NPs significantly reduced tumor growth, inhibited metastasis, and enhanced immune cell infiltration. The platform showed high biocompatibility, prolonged circulation time, and effective targeting, making it a promising multimodal therapy for NSCLC. This approach addresses the limitations of traditional treatments by combining PDT with immunotherapy, offering a less invasive, more effective, and safer alternative for NSCLC treatment.This study presents a novel nanoplatform, ICG@MnO₂@Exo-anti-PD-L1, for combined photodynamic therapy (PDT) and immunotherapy against non-small cell lung cancer (NSCLC). The platform consists of indocyanine green (ICG), a photosensitizer, encapsulated in hollow manganese dioxide (MnO₂) nanospheres, which are then enclosed in reprogrammed exosomes modified with anti-PD-L1 monoclonal antibodies. This design enables targeted delivery to PD-L1-expressing cancer cells, where the MnO₂ catalyzes the conversion of hydrogen peroxide (H₂O₂) to oxygen, alleviating tumor hypoxia. ICG generates singlet oxygen under near-infrared (NIR) irradiation, leading to tumor cell death. Additionally, MnO₂ is reduced to Mn²⁺, which polarizes macrophages from M2 to M1, enhancing T cell activation and immune response. The system effectively modulates the tumor microenvironment (TME), improving PDT efficiency and immunotherapy outcomes. In vitro and in vivo experiments demonstrated that ICG@MnO₂@Exo-anti-PD-L1 NPs significantly reduced tumor growth, inhibited metastasis, and enhanced immune cell infiltration. The platform showed high biocompatibility, prolonged circulation time, and effective targeting, making it a promising multimodal therapy for NSCLC. This approach addresses the limitations of traditional treatments by combining PDT with immunotherapy, offering a less invasive, more effective, and safer alternative for NSCLC treatment.