Heat stress caused by climate changes and global warming has become more frequent. Crop yield is usually quite sensitive to heat stress especially when it happens at reproductive stage. As evident by extensive yield loss in crops, the negative effects of heat stress on crops increased the risk of global food and nutrition security. In this chapter, we reviewed the current studies on the effects of heat stress on crops from morphological, physiological, biochemical, metabolic and molecular aspects. Moreover, we present approaches for increasing crop resilience at heat stress using conventional breeding methods, QTLs identification, transgenic methods, and multiomics (transcriptomic, proteomics, metabolomics and phenomics) approaches. The future work should consider the multiple abiotic stress or heat stress combined with biotic stress to efficiently ensure crop production and secure food supply in the future climate challenges. An integrated framework including traditional methods and advanced multiomics will help to understand the response of crops to heat stress and enhance thermotolerance of crops.