Abstract: Tumor ribonucleic acid (RNA) vaccines, which are emerging as promising cancer immunotherapies, have achieved significant technological breakthroughs during the COVID-19 pandemic. These vaccines activate immune responses through precise antigen expression. However, they face challenges such as suboptimal delivery efficiency and insufficient immunogenicity. Current studies focus on three design strategies: conventional messengerribonucleic acid (mRNA), self-amplifying mRNA, and circular RNA (circRNA) vaccines coupled with lipid nanoparticles (LNP) and polyethylene glycol (PEG) optimization for enhanced delivery. Clinical trials have demonstrated the synergistic efficacy of RNA vaccines in combination with immune checkpoint inhibitors, chemotherapy, or oncolytic viruses. However, clinical translation is hindered by the complexity of antigen selection and storage stability limitations. In this review, we systematically summarize the recent clinical advancements in tumor RNA vaccines, analyze their technical challenges, and propose innovative strategies to address the current therapeutic bottlenecks to guide future research and clinical applications.