<p>Wheat (<i>Triticum aestivum</i>) is among the most cultivated cereal crops vital to global food security. Drought stress driven by climate change significantly limits wheat production by adversely affecting important morphological, physiological, and biochemical processes. Understanding the adaptive responses of wheat to drought stress is important to develop the ability to create appropriate approaches. This review focuses on drought tolerance mechanisms such as proline accumulation, relative water content, chlorophyll retention, cell membrane stability, antioxidant defense responses, and molecular mechanisms. Similarly, sustainable resilience strategies, such as agronomic practices, advanced breeding methods including quantitative trait loci (QTL) mapping, clustered regularly interspaced short palindromic repeat (CRISPR-Cas9), and microbial approaches that include plant growth-promoting rhizobacteria (PGPR), are being used to mitigate yield losses resulting from drought stress. Furthermore, the emerging field of metabolomics is profiled for identifying drought-responsive biomarkers and determining metabolic pathways related to drought adaptability. Therefore, integrating molecular, microbial, and agronomic approaches can ultimately provide a cohesive approach to breeding drought-tolerant wheat varieties and supporting sustainable wheat production in water-limited environments in the future. Following these paths will help support food security in a world with climate change, ultimately enhancing wheat’s resilience to increasingly unpredictable weather conditions.</p>