Sesame (Sesamum indicum L.) is the most ancient oilseed crops cultivated by humans, widely known as the ’queen of oilseeds’ due to its high oil content, nutritional richness and health-promoting properties. The global demand for sesame has risen significantly in recent years, largely driven by its excellent oil quality, high protein levels, antioxidant compounds such as sesamin and sesamolin and its remarkable adaptability to a wide range of agro-climatic and soil conditions. Despite being widely grown and self-sustaining in terms of acreage, sesame continues to exhibit low average productivity. This is primarily due to limited genetic improvement, environmental stress susceptibility and poor adaptation to diverse agro-ecological regions. To overcome these challenges, genetic enhancement of sesame is essential. Recent advancements in molecular biology and genomics have opened new avenues for sesame improvement through the use of molecular markers, QTL mapping, mutation breeding and genome-assisted selection. This article aims to explore the genetic approaches currently employed in sesame crop improvement. It highlights the evolutionary history of sesame research, development and utilization of genetic resources, progress in molecular breeding and the challenges faced by breeders. Emphasis is also placed on prospects and the integration of modern biotechnological tools to enhance sesame productivity and resilience.