Sesame production is important in agriculture, food industry, and the crop diversity due to its rich nutritional profile and health benefits. Despite its significant value, sesame is still an orphan crop that has received little scientific attention, resulting in low yield compared to other major oilseed crops. This review offers a comprehensive overview of the present state of production, knowledge, and research advancements concerning Sesamum indicum on a global scale. The FAOSTAT database was extensively used to examine the global trends from 1961 to 2021. In the past 60 years, global sesame production has substantially increased, with Asia and Africa being the primary producers. The integration of omics technologies and biotechnological interventions has revolutionized our understanding of the genetic basis of sesame, enhanced productivity, invigorated stress resilience, and improved seed quality. High-throughput sequencing methods such as RNA-seq, RAD-seq, SLAF-seq, and GBS technology are used in various studies, linkage mapping, and identification of trait-associated markers. Fine linkage maps, and multi-omics studies such as genomics, proteomics, transcriptomics, and metabolomics have been employed in sesame research for gene and QTL mapping. Proteins and metabolic pathways related to oil content, yield, and stress tolerance were reported. Genes and QTLs related to yield and its components, drought, salt, and osmotic stress tolerance were discovered. Candidate genes associated with capsule shattering and seed shattering were recently revealed. For more achievement in sesame, it is important to enhance sesame production efficiency through mechanization, advanced agricultural practices, and knowledge dissemination to farmers. MAS and multi-omics integration should be particularly reinforced. The advancements in sesame production present a significant and promising opportunity for farmers, governments, and stakeholders in the agricultural sector.