Immunotherapy has revolutionized cancer treatment by using a patient’s own immune system to target and eradicate tumor cells. Therapeutic tumor vaccines, as one avenue in this emerging area, are designed to elicit antigen-specific antitumor immune responses. In this paper we provide a comprehensive summary on how our expanding knowledge of immune-oncology, genomics, and bioinformatics has led to novel, optimized cancer vaccine approaches. That together with rational and biology-driven combination of cancer vaccines with other therapeutic modalities has great potential to reshape the current immunotherapy field.