The groundbreaking success of messenger RNA (mRNA) vaccines during the COVID‐19 pandemic has significantly accelerated their application in oncology. This review comprehensively synthesizes the recent advancements in mRNA cancer vaccine development, emphasizing three critical domains: mechanistic innovations, clinical translation, and ongoing challenges. Technologically, advancements in nucleotide modification, lipid nanoparticle (LNP) delivery systems, and AI‐driven neoantigen selection have significantly improved vaccine stability, immunogenicity, and personalization. Clinically, more than 150 trials have demonstrated the synergistic efficacy of mRNA vaccines (e.g., mRNA‐4157/V940, BNT122) in combination with immune checkpoint inhibitors (ICIs), particularly in melanoma, with Phase Ⅲ trials currently underway. Individualized neoantigen vaccines targeting patient‐specific mutations have shown unprecedented response rates (> 50% in certain cohorts), while shared‐antigen vaccines are progressing for high‐incidence cancers. However, several critical challenges remain: (1) overcoming immunosuppressive tumor microenvironments (TME), (2) addressing systemic toxicities and LNP‐related limitations, (3) scaling up cost‐effective personalized manufacturing, and (4) optimizing targeted delivery. Future research directions encompass self‐amplifying mRNA constructs, novel biomaterial vectors, neoadjuvant applications, and multi‐omics integration for next‐generation vaccine development. With rapid industrialization and evolving regulatory frameworks, mRNA vaccines are well‐positioned to revolutionize precision cancer immunotherapy despite persistent translational barriers.

This review synthesizes a decade of advancements in nucleic acid therapeutics for liver diseases, incorporating bibliometric analysis and translational evaluation. The field has evolved from foundational viral vector engineering to precision genome editing and RNA-based modulation, with advancements in CRISPR-Cas9 and innovations in non-viral delivery systems. Our analysis highlights the concentrated research efforts made in metabolic disorders and hepatocellular carcinoma, and reveals an emerging emphasis on multifactorial pathologies. Although clinical milestones highlight important advancements in targeting strategies, significant challenges remain in immune compatibility and preclinical translation. The integration of computational modeling, human-relevant disease models, and combinatorial strategies places nucleic acid therapies in a unique position to tackle the evolving global liver disease burden through mechanism-driven interventions.