Cassava (Manihot esculenta Crantz), a ”miracle of the tropics,” is a critical component of the approaches to alleviate poverty, hunger, and malnutrition and increase livelihood security. Its high inherent photosynthetic efficiency and ability to sustain growth in challenging environments make it a potential food and nutrition security crop. However, water remains the most limiting factor for future cassava production, particularly under anticipated climatic variability. Though cassava is popularized as a drought-tolerant crop, seasonal or intermittent water stress episodes affect cassava productivity by influencing plant growth, storage root yield, and quality. Successful cassava production in drought-prone areas relies on the development of drought-tolerant cultivars along with tailored agronomic practices. We reviewed multi-faceted responses from morphological level to tissue/cell level biochemical changes, root development responses, and storage root quality alterations occurring under drought and potential targets for the future breeding program. This knowledge will pave the way for developing breeding strategies and implementable agronomic methods.