Nickel (Ni) is an essential micronutrient for plants, responsible for metabolizing urea nitrogen (urea-N) by urease and mitigating abiotic and oxidative stresses through the glyoxalase (Gly) and glutathione (GSH) cycles. However, excess Ni is toxic to flora at >100 mg kg−1, except for hyperaccumulators that tolerate >1000 mg kg−1 Ni. This review discusses the benefits of Ni nutrient management for soil fertility, improving food security, and minimizing adverse environmental impacts from urea overapplication. Many farming soils are Ni deficient, suggesting that applying 0.05–5 kg ha−1 of Ni improves yield and urea-N use efficiency. Applied foliar and soil Ni fertilizers decrease biotic stresses primarily by control of fungal diseases. The bioavailability of Ni is the limiting factor for urease synthesis in plants, animal guts, and the soil microbiome. Improved urease activity in plants and subsequently through feed in livestock guts reduces the release of nitrous oxide and nitrite pollutants. Fertilizer Ni applied to crops is dispersed in vegetative tissue since Ni is highly mobile in plants and is not accumulated in fruit or leafy tissues to cause health concerns for consumers. New methods for micronutrient delivery, including rhizophagy, recycled struvite, and nanoparticle fertilizers, can improve Ni bioavailability in farming systems.