Purpose <p>Extracellular vesicles (EVs) are cell-secreted, bionormal vesicles capable of homing to target cells via homologous targeting and evading immune clearance. However, their therapeutic use is limited by low yield and inefficient drug loading. In contrast, liposomes offer high drug-loading efficiency but face challenges such as poor tumor targeting and rapid immune clearance. To overcome these limitations, we developed a fusion nanoparticle delivery system by fusing EVs and liposomes, aiming to combine their respective advantages for enhanced cancer therapy.</p> Methods <p>Docetaxel-loaded liposomes were prepared via thin film hydration, while EVs were isolated from A549 cell-conditioned media using differential centrifugation. Fusion was achieved through a freeze–thaw method. The resulting vesicles were characterized for particle size distribution, encapsulation efficiency, and fusion system formation. In vitro assays included biocompatibility, cellular uptake, phagocytosis, and cytotoxicity, while in vivo antitumor efficacy was evaluated in an A549 tumor xenograft mouse model. Pharmacokinetic profiles were assessed in Sprague-Dawley rats.</p> Results <p>The fusion nanoparticles exhibited 3-fold higher uptake by parent cells and 1.5-fold lower phagocytosis compared to liposomes. Docetaxel-loaded fusion vesicles showed a 5-fold lower IC₅₀ in vitro. Pharmacokinetics study revealed a 1.33-fold longer half-life, 1.5-fold greater mean residence time, and a 2-fold increase in AUC over liposomes. The fusion system nearly doubled tumor growth inhibition compared to liposomes in vivo.</p> Conclusion <p>The EV–liposome fusion system effectively combines high drug-loading capacity with tumor-targeting capability, enhancing bioavailability and therapeutic efficacy. This platform presents a promising strategy for improving nanoparticle-based cancer treatment.</p>