Sorghum, the fifth most important crop globally, thrives in challenging environments such as arid, saline-alkaline, and infertile regions. This remarkable crop, one of the earliest crops domesticated by humans, offers high biomass and stress-specific properties that render it suitable for a variety of uses including food, feed, bioenergy, and biomaterials. What’s truly exciting is the extensive phenotypic variation in sorghum, particularly in traits related to growth, development, and stress resistance. This inherent adaptability makes sorghum a game-changer in agriculture. However, tapping into sorghum’s full potential requires unraveling the complex genetic networks that govern its key agricultural traits. Understanding these genetic mechanisms is paramount for improving traits such as yield, quality, and tolerance to drought and saline-alkaline conditions. This review provides a comprehensive overview of functionally characterized genes and regulatory networks associated with plant and panicle architectures, as well as stress resistance in sorghum. Armed with this knowledge, we can develop more resilient and productive sorghum varieties through cutting-edge breeding techniques like genome-wide selection, gene editing, and synthetic biology. These approaches facilitate the identification and manipulation of specific genes responsible for desirable traits, ultimately enhancing agricultural performance and adaptability in sorghum.