Extreme changes in weather including heat-wave and high-temperature fluctuations are predicted to increase in intensity and duration due to climate change. Wheat being a major staple crop is under severe threat of heat stress especially during the grain-filling stage. Widespread food insecurity underscores the critical need to comprehend crop responses to forthcoming climatic shifts, pivotal for devising adaptive strategies ensuring sustainable crop productivity. This review addresses insights concerning antioxidant, physiological, molecular impacts, tolerance mechanisms, and nanotechnology-based strategies and how wheat copes with heat stress at the reproductive stage. In this study stress resilience strategies were documented for sustainable grain production under heat stress at reproductive stage. Additionally, the mechanisms of heat resilience including gene expression, nanomaterials that trigger transcription factors, (HSPs) during stress, and physiological and antioxidant traits were explored. The most reliable method to improve plant resilience to heat stress must include nano-biotechnology-based strategies, such as the adoption of nano-fertilizers in climate-smart practices and the use of advanced molecular approaches. Notably, the novel resistance genes through advanced molecular approach and nanomaterials exhibit promise for incorporation into wheat cultivars, conferring resilience against imminent adverse environmental conditions. This review will help scientific communities in thermo-tolerance wheat cultivars and new emerging strategies to mitigate the deleterious impact of heat stress.