Extracellular vesicles (EVs) and liposomes are natural and synthetic drug delivery systems, respectively, with their own advantages and limitations. EV/liposome fusion allows the generation of hybrid EVs that benefit from both the versatility of liposomes (tunable lipid and protein composition, surface functionalization, lumen loading, etc.) and the functionality of EVs (natural targeting properties, low immunogenicity, anti-inflammatory properties, etc.). Here, we describe the methods to (1) produce EVs and liposomes, (2) induce and monitor their fusion, and (3) purify the obtained hybrid EVs.