The first priority of drug combination therapy in the treatment of cancer is to achieve enhanced therapeutic efficacy and reduced side effects. The main issue in drug combination therapy is the inscrutable interaction between different drug components. Herein, we developed a multicompartmentalized architecture as a new delivery system. A host liposome encapsulates multiple guest liposomes, where various drug components were loaded into disparate compartments separately. This strategy avoids the interaction among different components before their arrival at the targeting sites and provides the fixed drug combination ratio as needed. Doxorubicin (DOX) and 5-fluorouacil (5FU) loaded smaller liposomes were encapsulated into bigger liposomes with a fixed dose ratio of DOX to 5FU. In vivo tumor growth inhibition by vesosomes was evaluated in HeLa tumor-bearing nude mice, which confirms the enhancement of the delivery system on the synergism of the drug combination.