Heat stress as a yield limiting issue has become a major threat for food security as global warming progresses. Being sessile, plants cannot avoid heat stress. They respond to heat stress by activating complex molecular networks, such as signal transduction, metabolite production and expressions of heat stress-associated genes. Some plants have developed an intricate signalling network to respond and adapt it. Heat stress tolerance is a polygenic trait, which is regulated by various genes, transcriptional factors, proteins and hormones. Therefore, to improve heat stress tolerance, a sound knowledge of various mechanisms involved in the response to heat stress is required. The classical breeding methods employed to enhance heat stress tolerance has had limited success. In this era of genomics, next generation sequencing techniques, availability of genome sequences and advanced biotechnological tools open several windows of opportunities to improve heat stress tolerance in crop plants. This review discusses the potential of various functional genomic approaches, such as genome wide association studies, microarray, and suppression subtractive hybridization, in the process of discovering novel genes related to heat stress, and their functional validation using both reverse and forward genetic approaches. This review also discusses how these functionally validated genes can be used to improve heat stress tolerance through plant breeding, transgenics and genome editing approaches.