Updated project metadata. Drought and salinity reduce plant growth and grain yield in wheat. To explain the role of Cu and Fe NPs in the improvement of growth and yield of wheat varieties, gel-free proteomic technique was used. Spike length, number of grains per spike, and 100 grain weight were increased at 25 ppm Cu and Fe NPs in high yielding galaxy-13, drought tolerant Pakistan-13, and salinity tolerant NARC-11. A total of 86, 131, and 30 proteins were significantly changed in abundance under Cu and Fe NPs exposure. The number of proteins related to stress, proteins, and glycolysis were mainly changed by Cu and Fe NPs exposure. By Cu NPs, in galaxy-13 starch degradation and glycolysis pathway were increased, while decreased in Pakistan-13 and NARC-11. Furthermore, by Fe NPs, only in galaxy-13 tricarboxylic acid cycle was increased while did not change glycolysis and starch degradation. Uptake of Cu NPs increased at 25 ppm in galaxy-13, Pakistan-13 and NARC-11 while Fe NPs uptake increased only at 35 and 40 ppm in NARC-11.