The field experiment was carried out at the Agricultural Experimental Station of Desert Research Center, at New Valley Governorate during the winter seasons of 2022-2023 for the assessment of the contribution of nanoiron-metal organic frameworks and gallic acid for heat stress tolerance in two wheat cultivars (Giza 171 and Gemmeiza 12). Nano-organic frameworks of iron metal were synthesized, and through various activation processes and the use of high temperatures, gallic acid was introduced and bound into the nano-organic frameworks. Its synthesis and purity were also confirmed by characterizing it using HR-SEM, XRD, and FTIR. Treatment with nanoiron-metal organic frameworks conjugated with gallic acid (FeM4) contributed to alleviating the negative effects of heat stress on the metabolic products of wheat plants and protected them from adverse effects, and this was consistent with growth and yield. In this context, FeM4 had the best effect on improving the productivity of wheat yield by 4.3 and 5.4 times for Giza 171 and Gemmeiza 12, respectively, compared to the control. The increase in some biochemical constituents and the decrease in some other constituents had a role in alleviation negative effects of heat stress on metabolites and protection against the adverse effects of stress. FeM4 treatment led to an increase in the content of photosynthetic pigments, especially chlorophyll (a) by 1.55 times and chlorophyll (b) by 1.42 times, and a decrease in the content of compatible solutes such as proline by 59% and glycinebetaine by 23%, compared to the control. Likewise, the previous treatment led to an increase in the activity of peroxidase and superoxide dismutase enzymes in both wheat cultivars. In the molecular level (ISSR technique), treating the two wheat cultivars with nanoiron-metal organic frameworks and gallic acid did not lead to any noticeable changes in the genetic material. Applying these recommendations in new desert areas exposed to heat stress conditions could play a role in increasing the productivity of wheat cultivars (especially Giza 171), and this contributes to reducing the wheat nutritional gap in Egypt.