<p>Pearl millet (<i>Pennisetum glaucum</i> R. Br.), an important cereal crop widely grown in arid and semi-arid regions of Asia and Africa, plays a vital role in global food security. However, it faces significant challenges due to climate change, soil degradation, emerging pests, and diseases. Genetic enhancement is a promising approach to mitigate these challenges and to improve pearl millet resilience and yield. This review explores recent advancements in genetic enhancement to addresses key constraints in boosting pearl millet yields sustainably. The developments in genetic enhancement hold promise for addressing the complex challenges faced in pearl millet cultivation and offers the way forward for increased productivity, resilience, and food security in vulnerable regions. This review highlights modern strategies such as molecular breeding, genomic selection, systems biology tools, genetic engineering, and gene editing, which enable the precise identification and incorporation of desirable traits such as abiotic stress tolerance, resistance to biotic stress, improved nutritional content, etc. However, continued research, collaboration, and investment are essential to fully harness the potential of genetic resources and technologies to benefit smallholder farmers and global food and nutritional security.</p>