Neoantigen-based personalized vaccines have emerged as an important innovation in the field of precision oncology through utilizing unique tumor somatic mutations to stimulate a targeted anti-tumor immune response. Unlike common tumor antigens, neoantigens can be recognized by the immune system as foreign because they exist only on tumor cells and thus do not contribute to any autoimmune reactions as a result of central immune tolerance. The emergence of techniques in next-generation sequencing, mutational profiling, and bioinformatics has made it possible to precisely identify neoantigens. In addition, breakthroughs in vaccine technology, such as synthetic long peptides, dendritic cell vaccination, and nucleic acid vaccination, have facilitated its clinical application. Studies have shown that neoantigen-based personalized vaccines are safe and can induce potent T-cell-mediated anti-tumor immune responses, especially when combined with immune checkpoint inhibitors. Randomized trials have indicated their potential in decreasing cancer recurrence. There still remain some limitations in developing personalized neoantigen vaccines due to the problem of tumor heterogeneity, immune evasion, neoantigen prediction, immunosuppression environment in the tumors, and high cost and long manufacturing time for personalized vaccines. This paper provides an overview of current methods and new approaches for neoantigen identification and vaccine development.