Mother’s milk is widely recognized as an exclusive source of nutrients, particularly for premature infants. However, there are situations when mother’s own milk is inaccessible to newborns, in such cases, expressed milk from donor mothers is essential to cover the gaps. Human Milk Banks (HMBs) have been developed in several regions of the world to address such difficulties. Despite the fact that there are multiple active HMBs across the globe, there is a lack of comprehensive data on the relevance and operation of human milk banks across South Asian Countries (SACs) where the burden of infant death due to prematurity remains disproportionately high. Challenges like lack of technological facilities, funding channels and universal guidelines impede its full potential. Additional challenges include cultural beliefs, taboos, lack of awareness and knowledge also exacerbate such conditions. Therefore, there is an urgent need to comprehend the formation of universal guidelines and the recruitment of technical leaders for optimizing and promoting HMBs for fulfilling the needs of newborns. This review article addresses these issues in depth and discusses potential solutions to overcome such gaps.