SUMMARY Global wheat production amounted to >780 MMT during 2022–2023 whose market size are valued at >$128 billion. Wheat is highly susceptible to high‐temperature stress (HTS) throughout the life cycle and its yield declines 5–7% with the rise in each degree of temperature. Previously, we reported an array of HTS‐response markers from a resilient wheat cv. Unnat Halna and described their putative role in heat acclimation. To complement our previous results and identify the key determinants of thermotolerance, here we examined the cytoplasmic proteome of a sensitive cv. PBW343. The HTS‐triggered metabolite reprograming highlighted how proteostasis defects influence the formation of an integrated stress‐adaptive response. The proteomic analysis identified several promising HTS‐responsive proteins, including a NACα18 protein, designated TaNACα18, whose role in thermotolerance remains unknown. Dual localization of TaNACα18 suggests its crucial functions in the cytoplasm and nucleus. The homodimerization of TaNACα18 anticipated its function as a transcriptional coactivator. The complementation of TaNACα18 in yeast and overexpression in wheat demonstrated its role in thermotolerance across the kingdom. Altogether, our results suggest that TaNACα18 imparts tolerance through tight regulation of gene expression, cell wall remodeling and activation of cell defense responses.