Cardiometabolic diseases are major contributors to mortality and morbidity, and their burden displays global and regional disparities. Gene-environment interactions contribute to the pathogenesis of cardiometabolic diseases. Population differences in genetic structure, ancient environmental pressures that shape the human genome, and early life environmental adversities (e.g., in utero conditions) all contribute to observed disparities in global cardiometabolic diseases. The genetic and sociocultural diversity of global populations presents opportunities for discovering genomic loci that influence cardiometabolic diseases as illustrated by a few genetic, epigenetic, and population-genetic discoveries leading to notable understanding of disease mechanisms. However, African, Latin American and Hispanic, and indigenous peoples represent <4% of all genome-wide association study samples analyzed to date. Using examples of recent studies in African populations, we discuss the crucial importance of conducting genomic studies in ancestrally diverse populations to understand disease mechanisms and to prepare fertile ground for future delivery of precise health care to all individuals.