Cancer vaccine therapies targeting tumor-associated antigens have been extensively studied as immunotherapies that elicit antitumor immunity, but the results of clinical trials have been unsatisfactory. One of the causes of the failure was thought to be that the target antigens were not specific to the tumor and therefore were unable to induce an immune response that was sufficient for tumor control. Therefore, cancer vaccines targeting tumor-specific neoantigens have been developed. Since neoantigens, which are produced as a result of somatic mutations in tumor cells, are tumor-specific and are not present in normal cells, it is thought that they will induce a stronger tumor-specific immune response. Technological advances in recent years have enabled detailed immunological and biological analyses to be performed quickly and inexpensively, improving the accuracy of genomic sequencing and bioinformatics algorithms for epitope prediction. Clinical trials of personalized neoantigen-based vaccines have thus been conducted, with some promising results. In addition, several new attempts, such as the combination of neoantigen-based personalized vaccines and immune checkpoint inhibitors, have been studied. This chapter outlines the concept and procedure of neoantigen-based personalized cancer vaccines, the results of and issues with their clinical trials, and future challenges.