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Wheat is produced worldwide over six continents with the European Union, China, India, Russia, and the United States as major producer countries. The productivity was recorded 749 million tons by harvesting from 220-million-hectare land. It is the need of the hour to develop stress-tolerant wheat varieties to enhance the productivity by 60% to provide food security to 9.6 billion-world population by 2050. Although the genotypes have been identified for heat, drought and salt tolerance, their underlying mechanism for tolerance is poorly understood. The detailed understanding of the mechanism and identification of critical factors participating in multiple abiotic stress tolerance is essential. In the present study, the contrasting wheat genotypes were intensely characterized and assessed for the expression of different stress responsive genes under lab conditions. The expression analysis revealed that SHN1, DREB6, NHX2 and AVP1 were found to be highly induced under heat, salt and drought stresses in wheat. Thus, these genes can be used as signature genes to identify the multiple stress-tolerant varieties in the breeding program. The novel variants of these genes can be targeted through breeding or genetic engineering or genome editing strategies to develop multiple abiotic stress tolerant wheat varieties.