Sorghum (Sorghum bicolor L. Moench) is a crucial cereal crop for sustaining livelihood and economies globally across diverse agro-ecological regions. It is emerging as a model crop for functional genetics and genomics of tropical grasses with abundant uses, viz., food, feed, fodder and fuel. Originated in Africa thousands of years ago, sorghum has become a staple food for millions of people, particularly in arid and semi-arid climates where other cereal crops generally struggle to thrive. However, various abiotic stresses, including drought, salinity and temperature extremes like heat and cold, significantly affect sorghum production by compromising plant growth, development and yield potential, posing challenges to farmers and threatening food security in these regions. In recent years, omic technologies like genomics, transcriptomics, proteomics, metabolomics and phenomics emerged as powerful tools for unravelling the molecular mechanisms underlying stress responses in sorghum, which helps to develop effective strategies to mitigate stress effects and improve sorghum resilience in the near future. In this review, we will explore the application of omics data integration and systems biology to unravel complex stress networks, identification of stress-responsive genes and the potential of omics technologies towards resilience enhancement in the sorghum, which helps to ensure sustainable crop production to face of environmental challenges.