SUMMARYCrops often have to face several abiotic stresses simultaneously, and under these conditions, the plant's response significantly differs from that observed under a single stress. However, up to the present, most of the molecular markers identified for increasing plant stress tolerance have been characterized under single abiotic stresses, which explains the unexpected results found when plants are tested under real field conditions. One important regulator of the plant's responses to abiotic stresses is abscisic acid (ABA). The ABA signaling system engages many stress‐responsive genes, but many others do not respond to ABA treatments. Thus, the ABA‐independent pathway, which is still largely unknown, involves multiple signaling pathways and important molecular components necessary for the plant's adaptation to climate change. In the present study, ABA‐deficient tomato mutants (flacca, flc) were subjected to salinity, heat, or their combination. An in‐depth RNA‐seq analysis revealed that the combination of salinity and heat led to a strong reprogramming of the tomato transcriptome. Thus, of the 685 genes that were specifically regulated under this combination in our flc mutants, 463 genes were regulated by ABA‐independent systems. Among these genes, we identified six transcription factors (TFs) that were significantly regulated, belonging to the R2R3‐MYB family. A protein–protein interaction network showed that the TFs SlMYB50 and SlMYB86 were directly involved in the upregulation of the flavonol biosynthetic pathway‐related genes. One of the most novel findings of the study is the identification of the involvement of some important ABA‐independent TFs in the specific plant response to abiotic stress combination. Considering that ABA levels dramatically change in response to environmental factors, the study of ABA‐independent genes that are specifically regulated under stress combination may provide a remarkable tool for increasing plant resilience to climate change.