A gene-engineered exosome (PD1-Imi Exo) was developed to reverse T cell exhaustion in cancer immunotherapy. This exosome is designed by incorporating the PD1 gene into natural exosomes and simultaneously enveloping the immune adjuvant imiquimod. The exosome exhibits a round vesicular shape (approximately 139 nm), shows strong targeting and binding to both cancer cells and dendritic cells, and demonstrates significant therapeutic efficacy in melanoma and breast cancer models. The mechanism involves blocking the PD1/PDL1 immune checkpoint, which prevents T cell exhaustion, and promoting the maturation of immature dendritic cells through imiquimod, thereby restoring CD8+ T cell function. The exosome effectively enhances the immune response by reactivating CD8+ T cells and improving the overall prognosis of cancer patients. The study provides a promising strategy for enhancing PD1/PDL1 therapy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity. The exosome shows improved targeting, binding, and stability, with a high encapsulation efficiency of imiquimod and a sustained release profile. The results demonstrate that PD1-Imi Exo significantly inhibits tumor growth and improves survival rates in melanoma and breast cancer models, indicating its potential as a novel therapeutic approach in cancer immunotherapy.A gene-engineered exosome (PD1-Imi Exo) was developed to reverse T cell exhaustion in cancer immunotherapy. This exosome is designed by incorporating the PD1 gene into natural exosomes and simultaneously enveloping the immune adjuvant imiquimod. The exosome exhibits a round vesicular shape (approximately 139 nm), shows strong targeting and binding to both cancer cells and dendritic cells, and demonstrates significant therapeutic efficacy in melanoma and breast cancer models. The mechanism involves blocking the PD1/PDL1 immune checkpoint, which prevents T cell exhaustion, and promoting the maturation of immature dendritic cells through imiquimod, thereby restoring CD8+ T cell function. The exosome effectively enhances the immune response by reactivating CD8+ T cells and improving the overall prognosis of cancer patients. The study provides a promising strategy for enhancing PD1/PDL1 therapy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity. The exosome shows improved targeting, binding, and stability, with a high encapsulation efficiency of imiquimod and a sustained release profile. The results demonstrate that PD1-Imi Exo significantly inhibits tumor growth and improves survival rates in melanoma and breast cancer models, indicating its potential as a novel therapeutic approach in cancer immunotherapy.