Global crop productivity is increasingly threatened by climate change, with drought stress (DS) a severe and escalating challenge to food security. Therefore, developing resilient crops is crucial for sustainable agriculture. Recent research has transitioned from examining general responses, such as hormonal imbalances, photosynthetic inhibition, and oxidative damage, to elucidating the intricate adaptive mechanisms, including signal transduction pathways and stress-responsive gene networks. Advances in omics technologies have significantly enhanced our understanding of plant responses to DS. Techniques such as genomics, transcriptomics, proteomics, and metabolomics have facilitated the dissection of drought-responsive genes, metabolic pathways, and regulatory networks, thereby contributing to the development of drought-resilient crops. This review synthesizes recent advancements in omics to provide a comprehensive analysis of the DS tolerance mechanisms in plants. It also explores the emerging potential of single-cell omics and artificial intelligence in deciphering the complex plant responses to DS. Finally, it evaluates the challenges associated with omics and outlines strategies to translate omics insights into the development of drought-resilient crops, ultimately enhancing crop productivity and food security.