Sorghum (Sorghum bicolor) has been a staple food in semiarid regions of Africa, Asia, and Central America and ranks as the fifth most produced crop worldwide. Its global adoption is rising due to its versatile nutritional and agronomic traits, positioning it as a key cereal for addressing the food challenges of a rapidly globalizing world. Omics technologies have revolutionized the study of sorghum, providing comprehensive insights into its climate resilience and nutritional quality. Genomics, proteomics, and metabolomics are essential for identifying key genes, regulatory networks, stress-responsive proteins, enzymatic pathways, and metabolic biomarkers that can be directly linked to the plant phenotype. These techniques provide a better understanding of sorghum’s response to climate stress while optimizing breeding strategies to enhance its nutritional quality. Individual and integrated omics analyses drive innovations in sorghum-based food systems, enhancing its potential as a sustainable crop, particularly in regions vulnerable to climate change. In this way, multi-omics approaches associated with bioinformatic and machine learning enable the selection of high-yield and climate-resilient species, supporting breeding programs towards high-nutritional sorghum genotypes. This chapter explores sorghum from its origins to the latest advances in breeding and omics technologies, offering a comprehensive overview to support sustainable cultivation and utilization under the imposed changes of climate conditions.