<p>Transformational advances in genomic sequencing capabilities, vastly improved HLA class I epitope prediction algorithms and powerful delivery platforms have facilitated the clinical development of vaccines targeting neoantigens encoded by tumor mutations. Early clinical trials indicate that vaccination against neoantigens can induce robust and durable T cell immunity that may persist for decades. mRNA vaccines, originally developed for cancer applications, have demonstrated considerable promise due to their efficacy and scalable production, as evidenced during the SARS-CoV-2 pandemic. However, the optimal cancer vaccine platform and delivery strategy is not yet known, as current approaches have not been compared head-to-head and substantial technological advances to improve immunogenicity and potentially clinical efficacy are achievable. For example, lipid-based formulations, while necessary for the effective delivery of mRNA vaccines, may also improve the immunogenicity of peptides and other delivery strategies. Here we review the current state of neoantigen vaccines in the clinic and highlight emerging opportunities for advancement in the field.</p>