Background <p>Aging is a complex biological process influenced by genetic, epigenetic, and environmental factors. Recent advances in nutritional geroscience and epigenomics have revealed that vitamins and plant polyphenols play critical roles in modulating epigenetic mechanisms that regulate aging and age-related diseases.</p> Purpose <p>This review aims to elucidate the synergistic effects of vitamin and plant polyphenol combinations on epigenetic regulation of aging, highlighting molecular mechanisms, clinical evidence, and the potential for precision nutrition strategies tailored to individual epigenetic profiles.</p> Main body <p>Vitamins act as essential cofactors in enzymatic reactions that influence DNA methylation and histone modifications, while polyphenols modulate transcription factors and cellular stress responses. Their combined administration enhances bioavailability and stability, enabling superior modulation of key aging pathways such as sirtuin signaling, autophagy, and oxidative stress responses. Evidence from multi-omics studies and clinical trials supports specific synergistic pairs including vitamin C with flavonoids, vitamin D with resveratrol, B-complex vitamins with polyphenolic acids, and vitamin E with catechins. These interactions promote beneficial epigenetic remodeling, reduce inflammaging, and improve biomarkers of healthy aging. Advances in machine learning and delivery technologies further facilitate personalized interventions.</p> Conclusion <p>Vitamin-polyphenol synergies represent a promising paradigm in precision nutrigeromics, offering a mechanistic basis for novel anti-aging strategies. Future research should focus on standardized assessment methodologies, long-term clinical validation, and optimized delivery systems to fully harness their therapeutic potential in extending healthspan.</p> Graphical Abstract <p></p>