<p>Obesity, diabetes and cardiovascular disease are rising rapidly in Asia. Population-based data consistently show that Asians are at higher risk for these non-communicable diseases than their European counterparts, especially when living in urban and migrant settings. Contrary to initial hypotheses, genetic susceptibility factors only partially explain globally divergent health outcomes. In this Perspective, we discuss potential additional mechanisms to explain this divergence. We review the global disparities in the cardiometabolic disease burden and the role of genetic variation. We then summarize potential pathways linking prenatal and postnatal adversity with unfavourable nutrition, increased adiposity and altered metabolic well-being in Asian populations. In parallel, molecular epidemiological studies are providing insights into how life-course exposures and environmental adversity intersect with adverse nutrition to establish the functional genomic changes that may drive cardiometabolic risk in global Asian populations. We highlight opportunities in precision health studies to advance Asian health through the identification of underlying aetiology critical to the development of effective interventions to promote and maintain metabolic health in current and future generations of Asian individuals worldwide.</p>