Multi-omics analysis of 495 participants from long-lived families identified 19 specific biomarkers—10 metabolites and 9 proteins—associated with familial longevity and a remarkable 13-year delay in cardiometabolic disease onset. Individuals from families with exceptional longevity showed reduced levels of inflammation markers like quinolinic acid and asymmetric dimethylarginine, along with preserved endothelial function indicated by elevated 6-keto-PGF1a and optimized extracellular matrix integrity through lower prolylhydroxyproline levels. The protein signatures revealed coordinated regulation of immune function, tissue remodeling, and regenerative capacity. This represents a significant advance in longevity research by providing the first comprehensive molecular portrait of inherited health advantages. The convergence on amino acid metabolism, lipid signaling, and inflammatory pathways offers concrete targets for interventions aimed at extending healthspan. However, this preprint awaits peer review, and the observational design cannot establish whether these biomarkers are causes or consequences of longevity. The findings may prove paradigm-shifting for precision medicine approaches to healthy aging.