Vesicles represent an important class of nanoscale drug delivery vehicles. To significantly reduce the time and resources that are required to optimize these drug carriers, this review article discusses the mathematical models that have been derived for understanding the formation of vesicles and their stability, as well as for predicting drug loading and their release. With regard to vesicle formation and stability, the packing parameter can be used to predict how the solution environment, surfactant composition, and surfactant molecular architecture can influence the supermolecular self-assembled structures that are formed from amphiphiles. In the context of drug delivery, this is useful for facilitating vesicle formation and stability during transit through the body. At the target site, this information can be used to help trigger a rapid release of the drug. With regard to drug loading, kinetic and equilibrium models provide guidelines for appropriate pH conditions and drug incubation times during loading. The diffusivity, partition coefficient, and bilayer thickness also play significant roles during loading and release of the drug. Our hope is that more researchers in this exciting field will complement their experimental approaches with these mathematical models to more efficiently develop vesicle-based drug carriers.