Wheat is among the most produced grain crops of the world and alone provides a fifth of the world's calories and protein. Wheat has played a key role in food security since the crop served as a Neolithic founder crop for the establishment of world agriculture. Projections showing a decline in global wheat yields in changing climates imply that food security targets could be jeopardized. Increased frequency and intensity of drought occurrence is evident in major wheat-producing regions worldwide, and notably, the wheat-producing area under drought is projected to swell globally by 60% by the end of the 21st century. Wheat yields are significantly reduced due to changes in plant morphological, physiological, biochemical, and molecular activities in response to drought stress. Advances in wheat genetics, multi-omics technologies and plant phenotyping have enhanced the understanding of crop responses to drought conditions. Research has elucidated key genomic regions, candidate genes, signalling molecules and associated networks that orchestrate tolerance mechanisms under drought stress. Robust and low-cost selection tools are now available in wheat for screening genetic variations for drought tolerance traits. New breeding techniques and selection tools open a unique opportunity to tailor future wheat crop with optimal trait combinations that help withstand extreme drought. Adoption of the new wheat varieties will increase crop diversity in rain-fed agriculture and ensure sustainable improvements in crop yields to safeguard the world's food security in drier environments.