Wheat is one of the stable food crops, has low zinc (Zn) concentration in grain generally, thus biofortification of Zn in wheat grain has attracted great attention in recent years. Nitrogen (N) and phosphorus (P) fertilization are common practices to harvest high crop yield, and also bring about influence on crop Zn nutrition. This review focuses on N and P fertilization on soil Zn availability and wheat Zn uptake and utilization 1) to evaluate N and P fertilization on grain Zn concentration and bioavailability, and 2) to explore the possibility of improving grain Zn nutrition by optimizing N and P management. Nitrogen fertilization increased grain Zn concentration and bioavailability. Soil Zn available increased by N fertilization, and it also enhanced root uptake, root to shoot translocation and remobilization from vegetative parts to grain, due to that various proteins and nitrogenous compounds played important roles in Zn uptake, translocation and remobilization. Phosphorus fertilization decreased grain Zn concentration and bioavailability on soil with low available P. Soil available Zn did not decrease by P fertilization when available P was lower than 34 and 200 mg kg^-1 in acid and calcareous soil. At lower P rate, wheat Zn uptake also did not reduce, and even increased Zn remobilization from vegetative parts to grain resulting in grain Zn uptake increase. The decrease in grain Zn concentration was mainly ascribed to the dilution effect caused by much more grain yield increase. In China, fertilizer input is undergoing a transformation from the overuse to reasonable input. Optimal N management by decreased N fertilization rate with high grain yield might lead grain Zn decrease in Zn-deficient soil, and optimal P management was required to harvest more grain Zn with high grain yield in wheat-dominant areas. In order to harvest 40 mg kg^-1 required for human health, apart from N and P management, Zn supplementation to soil or foliar should not neglect in wheat grain.