With the research progress and clinical application of immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies, immunotherapy has substantially changed the treating modalities for various tumors. Tumor neoantigen vaccines, as a promising immunotherapy method, aim to trigger a novel T cell response against neoantigens. Neoantigens, with their high specificity, can induce and expand the tumor-specific T cell receptor repertoire, which were discovered through the second-generation sequencing of DNA extracted from both the patient’s tumor and non-tumor tissue samples. The sequences and HLA types are then analyzed for alignment to pinpoint tumor-specific mutations. To validate the significance of these mutations, RNA sequencing data are integrated with the results. Subsequently, bioinformatics platforms are employed for the prediction and analysis of neoantigens encoded by mutated genes and HLA types, enabling the identification of potential immunogenic neoantigens. Finally, the immunogenicity of these neoantigens is assessed through techniques such as ELISPOT and tetramer assays. Tumor vaccines can be categorized as peptide-based, DNA-based, RNA-based, and DC-based products. Viruses, lipid nanoparticles, and nano delivery systems can activate antigen-presenting cells, enhancing their ability to recognize and present tumor-associated antigens, thus promoting the activation of CD8⁺ T cells. Neoantigen vaccines can be administered through various routes, including subcutaneous injection, intramuscular injection, intraperitoneal injection, intradermal injection, intravenous injection, or intralymphatic injection. Preliminary clinical studies have shown that neoantigen tumor vaccines have demonstrated evidence of strong tumor-specific immunogenicity and antitumor activity. In this review, we summarize in detail the source, prediction, and identification of tumor neoantigens, as well as the classification and immunization scheme of neoantigen vaccines. In addition, we highlight strategies for optimizing tumor neoantigen vaccines, including prediction algorithms, expressing multiple epitope structures, increasing immunogenicity, administration methods and delivery systems, and combining adjuvants and various treatments, providing new insights for the development of personalized immunotherapy.