Polymersomes self-assembled from amphiphilic macromolecules have attracted growing attention because of their multifunctionality and stability. By controlling the structural characteristics of polymersomes, including vesicle shape, size, and membrane thickness, their mechanical and transport properties as well as their fusion behavior can be manipulated. Numerous experimental techniques have been developed to explore polymersome characteristics; however, experimental microscopic observations and knowledge of vesicles are limited. Mesoscale simulations can complement experimental studies of the vesicular features at the microscopic level and thus provide a feasible method to better understand the relationship between the fundamental structures and physicochemical properties of polymersomes. Moreover, the predictive ability of the simulation approaches may greatly assist developments and future applications of polymersomes.