Abstract: Cancer nucleic acid vaccines activate specific antitumor immunity by delivering nucleic acid sequences encoding tumor antigens and have emerged as a promising approach in precision cancer immunotherapy. Compared with conventional protein-based and cell-based vaccines, nucleic acid vaccines offer advantages including flexible design, rapid manufacturing, and feasibility for personalized development. The clinical application of COVID-19 mRNA vaccines has facilitated advances in nucleoside modification technologies and lipid nanoparticle delivery platforms, supporting the translation of therapeutic cancer vaccines. Integration of high-throughput sequencing with artificial intelligence-based neoantigen identification has promoted the transition of cancer vaccines from empirical design toward precision personalized immunotherapy. Currently, multiple cancer nucleic acid vaccines have entered clinical studies in melanoma, pancreatic cancer, non-small cell lung cancer, and other malignancies, demonstrating favorable immunogenicity and therapeutic potential. Personalized mRNA vaccines combined with immune checkpoint inhibitors are being investigated in clinical settings, with application strategies expanding from treatment of advanced disease toward adjuvant therapy and minimal residual disease intervention. This review summarizes the key technological advances and clinical progress of cancer nucleic acid vaccines, discusses current challenges including neoantigen prediction accuracy, delivery efficiency, and immunosuppressive tumor microenvironment, and highlights future directions involving artificial intelligence-assisted antigen design and combination therapeutic strategies.