South Asians, comprising almost one fourth of the world population, are at higher risk of type 2 diabetes mellitus, hypertension, cardiovascular disease, and CKD compared with other ethnic groups. This has major public health implications in South Asia and in other parts of the world to where South Asians have immigrated. The interplay of various modifiable and nonmodifiable risk factors confers this risk. Traditional models of cardiometabolic disease progression and CKD evaluation may not be applicable in this population with a unique genetic predisposition and phenotype. A wider understanding of dietary and lifestyle influences, genetic and metabolic risk factors, and the pitfalls of conventional equations estimating kidney function in this population are required in providing care for kidney diseases. Targeted screening of this population for metabolic and vascular risk factors and individualized management plan for disease management may be necessary. Addressing unhealthy dietary patterns, promoting physical activity, and medication management that adheres to cultural factors are crucial steps to mitigate the risk of cardiovascular disease and CKD in this population. In South Asian countries, a large rural and urban community-based multipronged approach using polypills and community health workers to decrease the incidence of these diseases may be cost-effective.