In recent years, nanoparticles derived from cellular membranes have been increasingly explored for the prevention and treatment of human disease. With their flexible design and ability to interface effectively with the surrounding environment, these biomimetic nanoparticles can outperform their traditional synthetic counterparts. As their popularity has increased, researchers have developed novel ways to modify the nanoparticle surface to introduce new or enhanced capabilities. Moving beyond naturally occurring materials derived from wild-type cells, genetic manipulation has proven to be a robust and flexible method by which nanoformulations with augmented functionalities can be generated. In this review, an overview of genetic engineering approaches to express novel surface proteins is provided, followed by a discussion on the various biomedical applications of genetically modified cellular nanoparticles.