Sesame seeds and their edible oil are highly nutritious and rich in mono- and polyunsaturated fatty acids. Bioactive compounds such as sterols, tocopherols, and sesamol provide significant medicinal benefits. The high oil content (50%) and favorable mono- and polyunsaturated fatty acid balance, as well as resilience to water stress, make sesame a promising candidate crop for global agricultural expansion. However, sesame production faces challenges such as low yields, poor response to agricultural inputs, and losses due to capsule dehiscence. To enhance yield, traits like determinate growth, dwarfism, a high harvest index, non-shattering capsules, disease resistance, and photoperiod sensitivity are needed. These traits can be achieved through variation or induced mutation breeding. Crossbreeding methods often result in unwanted genetic changes. The gene editing CRISPR/Cas9 technology has the potential to suppress detrimental alleles and improve the fatty acid profile by inhibiting polyunsaturated fatty acid biosynthesis. Even though sesame is an orphan crop, it has entered the genomic era, with available sequences assisting molecular breeding efforts. This progress aids in associating single-nucleotide polymorphisms (SNPs) and simple sequence repeats (SSR) with key economic traits, as well as identifying genes related to adaptability, oil production, fatty acid synthesis, and photosynthesis. Additionally, transcriptomic research can reveal genes involved in abiotic stress responses and adaptation to diverse climates. The mapping of quantitative trait loci (QTL) can identify loci linked to key traits such as capsule size, seed count per capsule, and capsule number per plant. This article reviews recent advances in sesame breeding, discusses ongoing challenges, and explores potential strategies for future improvement. Hence, integrating advanced genomic tools and breeding strategies provides promising ways to enhance sesame production to meet global demands.