Soil contamination with chromium (Cr) is becoming a primary ecological and health concern, specifically in the Kasur and Sialkot regions of Pakistan. The main objective of the current study was to evaluate the impact of foliar application of zinc oxide nanoparticles (ZnO NPs) (0, 25, 50, 100 mg L−1) and Fe NPs (0, 5, 10, 20 mg L−1) in red sails lettuce plants grown in Cr-contaminated soil. Our results showed that both ZnO and Fe NPs improved plant growth, and photosynthetic attributes by minimizing oxidative stress in lettuce plants through the stimulation of antioxidant enzyme activities. At ZnO NPs (100 mgL−1), dry weights of shoots and roots and fresh weights of shoots and roots were improved by 53%, 58%, 34%, and 45%, respectively, as compared to the respective control plants. The Fe NPs treatment (20 mgL−1) increased the dry weight of shoots and the roots and fresh weights of shoots and roots by 53%, 76%, 42%, and 70%, respectively. Application of both NPs reduced the oxidative stress caused by Cr, as evident by the findings of the current study, i.e., at the ZnO NPs (100 mgL−1) and Fe NPs (20 mgL−1), the EL declined by 32% and 44%, respectively, in comparison with respective control plants. Moreover, Fe and ZnO NPs enhanced the Fe and Zn contents in red sails lettuce plants. Application of ZnO NPs at 100 mg L−1 and Fe NPs at 20 mg L−1, improved the Zn and Fe contents in plant leaves by 86%, and 68%, respectively, as compared to the control plants. This showed that the exogenous application of these NPs helped in Zn and Fe fortification in plants. At similar of concenteration ZnO NPs, CAT and APX activities were improved by 52% and 53%, respectively. Similarly, the POD contents were improved by 17% and 45% at 5 and 10 mg/L of Fe NPs. Furthermore, ZnO and Fe NPs limited the Cr uptake by plants, and the concentration of Cr in the leaves of lettuce was under the threshold limit. The exogenous application of ZnO NPs (100 mg L−1) and Fe NPs (20 mg L−1) reduced the Cr uptake in the leaves of red sails lettuce by 57% and 51%, respectively. In conclusion, ZnO and Fe NPs could be used for the improvement of plant growth and biomass as well as nutrient fortification in stressed environments. These findings not only underscore the efficacy of nanoparticle-assisted phytoremediation but also highlight its broader implications for sustainable agriculture and environmental health. However, future studies on other crops with molecular-level investigations are recommended for the validation of the results. HIGHLIGHTS: ZnO and Fe NPs improved the growth and photosynthesis of red sails lettuce plants Both NPs enhanced antioxidants enzymes activities in stressed plants NPs mediated response reduced the oxidative stress and Cr uptake in red sails lettuce ZnO and Fe NPs resulted in Zn and Fe fortification, respectively, in red sails lettuce [ABSTRACT FROM AUTHOR]