Therapeutic cancer vaccines aim to expand and activate antigen-specific T cells for the targeted elimination of cancer cells. While early clinical trials faced challenges due to suboptimal antigen-specific T-cell activation, recent advancements in antigen discovery and vaccine platform engineering have revitalized the field. This review provides a comprehensive overview of key tumor antigens, including tumor-associated antigens, viral oncoprotein antigens, neoantigens, and cryptic antigens, with a focus on their immunogenicity and therapeutic potential. Advances in our understanding of traditional cancer vaccination targets, in conjunction with the timely identification of novel antigen epitopes, have facilitated the strategic selection of vaccination targets. We also discuss the evolution of cancer vaccine platforms-spanning peptide-based formulations to advanced mRNA vectors-emphasizing innovative strategies to optimize antigen delivery efficiency and adjuvant effects. Efficient antigen delivery and adjuvant selection overcome immune tolerance and tumor-induced immunosuppression. Furthermore, we examine recent clinical trial data and emerging combination approaches that integrate cancer vaccines with other immunotherapies to increase efficacy. While significant progress has been made, challenges remain in improving vaccine-induced T-cell responses, overcoming immune suppression, and translating these advances into effective clinical interventions. Addressing these hurdles will be critical for realizing the full potential of cancer vaccines in immunotherapy.