Drought stress is a formidable challenge to agriculture and threatens food security and ecosystems. This chapter systematically examines the physiological, biochemical, and molecular responses of plants under water deficit conditions. Among the molecular mechanisms governing drought stress responses, we surveyed plants innate mechanisms against water scarcity in soil, moreover the complex signaling pathways, gene expression patterns, and metabolic adjustments that allow plants to adapt and survive in water-deficient environments were discussed in detail. Recent advancements in the identification and characterization of drought-responsive genes and proteins and potential targets for genetic engineering to enhance drought tolerance have been summed up. This chapter also summarized a range of mitigation approaches to alleviate the impact of drought on plant growth and productivity. Including traditional practices for cutting-edge biotechnological interventions, we assessed the potential of various strategies for enhancing water use efficiency and drought resilience in diverse plant species. We also highlight the promising prospects including omics and other molecular approaches and challenges associated with the implementation of these mitigation measures in global agricultural settings. This chapter aims to provide a holistic understanding of the complex responses of plants to drought stress and advancements in landscape mitigation strategies. In doing so, it contributes to the ongoing discourse on sustainable agriculture and encourages the development of innovative approaches to ensure global food security in the face of changing climatic conditions.