In this research, zinc oxide nanoparticles (ZnO NPs) are bio-synthesized using Mangifera indica leaf extract as a sustainable capping and stabilizing source. The spherical morphology, crystallinity, and average size (17.97 nm) of the ZnO NPs are examined through field emission scanning electron microscopy (ESEM), high-resolution transmission microscopy (HRTEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The hexagonal Zn2+ ion array in the wurtzite structure includes zinc atoms and numerous nearest-neighboring O2− ions, with an energy peak at 531.8 eV. The interactive roles of ZnO NPs and strigolactone (SL) in controlling cadmium (Cd) stress are studied in relation to morphological, biochemical, and physiological processes of the tomato plants. Cd exposure significantly lowers the growth, biomass, and total chlorophyll (48.39%) in tomato plants with the reduced activities of both enzymatic and non-enzymatic antioxidants. In contrast, such exposure increases metal translocation (58.00%), net photosynthesis (54.40%), and gas exchange parameters with enhanced levels of proline (83.94%), glycine betaine (72.95%), malondialdehyde (69.52%), hydrogen peroxide (97.82%), and electrolyte leakage (72.54%). Overall, the synergistic combination of ZnO NPs and SL should improve the growth, pigment content, photosynthesis, and antioxidant system of tomato plants, with increased levels of osmolytes to help maintain the water balance under stress.