A hybrid exosome system combining mesenchymal stem cell (MSC) exosomes with folate-targeted liposomes was developed to enhance the delivery of paclitaxel (PTX) for cancer therapy. This system significantly improved drug loading capacity and tumor targeting efficiency. In vitro studies showed that the hybrid exosomes (ELP) effectively delivered PTX to tumor cells, inducing apoptosis. In vivo experiments using a CT26 tumor model demonstrated that ELP significantly suppressed tumor growth and prolonged mouse survival. ELP treatment activated CD4⁺ and CD8⁺ T cells, reduced M2-type tumor-associated macrophages, and increased M1-type macrophages, while decreasing regulatory T cells. The hybrid system also enhanced the activation of dendritic cells and reduced the influence of regulatory T cells, promoting an anti-tumor immune response. The study highlights the therapeutic potential of ELP in cancer treatment, offering a promising approach for improving drug delivery and modulating the tumor microenvironment. The hybrid exosome-liposome system shows improved stability and drug-loading capacity compared to traditional exosomes, making it a valuable tool for future cancer therapies.A hybrid exosome system combining mesenchymal stem cell (MSC) exosomes with folate-targeted liposomes was developed to enhance the delivery of paclitaxel (PTX) for cancer therapy. This system significantly improved drug loading capacity and tumor targeting efficiency. In vitro studies showed that the hybrid exosomes (ELP) effectively delivered PTX to tumor cells, inducing apoptosis. In vivo experiments using a CT26 tumor model demonstrated that ELP significantly suppressed tumor growth and prolonged mouse survival. ELP treatment activated CD4⁺ and CD8⁺ T cells, reduced M2-type tumor-associated macrophages, and increased M1-type macrophages, while decreasing regulatory T cells. The hybrid system also enhanced the activation of dendritic cells and reduced the influence of regulatory T cells, promoting an anti-tumor immune response. The study highlights the therapeutic potential of ELP in cancer treatment, offering a promising approach for improving drug delivery and modulating the tumor microenvironment. The hybrid exosome-liposome system shows improved stability and drug-loading capacity compared to traditional exosomes, making it a valuable tool for future cancer therapies.