The induction of a robust and durable adaptive antitumor immune response with mRNA vaccines can be enhanced in several ways, highlighting the flexibility of the platform. These include delivery of lipid adjuvants within the nanoparticle; targeting multiple target antigen types, including those that are tumor–associated and tumor–specific antigens, such as neoantigens, and CAR T cell targets; employing cytokines or chemokines; and encoding or co-delivering immunostimulatory molecules and immunosuppressive inhibitors. These strategies should not only induce high-quality antigen-specific T cells, but also reprogram the tumor microenvironment in favor of a robust and durable anticancer response.