Global food crisis due to climate change, pandemic COVID-19 outbreak, and Russia-Ukraine conflict leads to catastrophic consequences; almost 10 percent of the world’s population go to bed hungry daily. Narrative solution for green agriculture with high vegetation and crop yield is mandatory; novel nanomaterials can improve plant immunity and restrain plant diseases. Iron is fundamental nutrient element; it plays vital role in enzyme activity and RNA synthesis; furthermore it is involved in photosynthesis electron-transfer chains. This study reports on the facile synthesis of colloidal ferric oxide nanoparticles as novel nano-fertilizer to promote vegetation and to suppress Fusarium wilt disease in tomato plant. Disease index, protection percent, photosynthetic pigments, and metabolic indicators of resistance in plant as response to induction of systemic resistance (SR) were recorded. Results illustrated that Fe2O3 NPs had antifungal activity against F. oxysporum. Fe2O3 NPs (at 20 µg/mL) was the best treatment and reduced percent disease indexes by 15.62 and gave highly protection against disease by 82.15% relative to untreated infected plants. Fe2O3 NPs treatments in either (non-infected or infected) plants showed improvements in photosynthetic pigments, osmolytes, and antioxidant enzymes activity. The beneficial effects of the synthesized Fe2O3 NPs were extended to increase not only photosynthetic pigments, osmolytes contents but also the activities of peroxidase (POD), polyphenol oxidase (PPO), catalase (CAT) and superoxide dismutase (SOD), enzymes of the healthy and infected tomato plants in comparison with control. For, peroxidase and polyphenol oxidase activities it was found that, application of Fe2O3 NPs (10 µg/mL) on challenged plants offered the best treatments which increased the activities of POD by (34.4%) and PPO by (31.24%). On the other hand, application of Fe2O3 NPs (20 µg/mL) on challenged plants offered the best treatments which increased the activities of CAT by (30.9%), and SOD by (31.33%).