Neoantigens, presented as peptides on the surfaces of cancer cells, have recently been proposed as optimal targets for immunotherapy in clinical practice. The promising outcomes of neoantigen-based cancer vaccines have inspired enthusiasm for their broader clinical applications. However, the individualized tumor-specific antigens (TSA) entail considerable costs and time due to the variable immunogenicity and response rates of these neoantigens-based vaccines, influenced by factors such as neoantigen response, vaccine types, and combination therapy. Given the crucial role of neoantigen efficacy, a number of bioinformatics algorithms and pipelines have been developed to improve the accuracy rate of prediction through considering a series of factors involving in HLA-peptide-TCR complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. On the other hand, shared neoantigens, originating from driver mutations at hot mutation spots (e.g., KRASG12D), offer a promising and ideal target for the development of therapeutic cancer vaccines. A series of clinical practices have established the efficacy of these vaccines in patients with distinct HLA haplotypes. Moreover, increasing evidence demonstrated that a combination of tumor associated antigens (TAAs) and neoantigens can also improve the prognosis, thus expand the repertoire of shared neoantigens for cancer vaccines. In this review, we provide an overview of the complex process involved in identifying personalized neoantigens, their clinical applications, advances in vaccine technology, and explore the therapeutic potential of shared neoantigen strategies.