To better understand effects of agronomic practices on yield-nutrition relationships in wheat (Triticum aestivum L.) grains for Zn biofortification while improving yields simultaneously, effects of different soil fertilization and different drone-based foliar spraying treatments were investigated. The mixture of Zn or increasing N but simultaneously reducing P in compound fertilizers were all practical to increase grain yields and Zn concentrations in calcareous soils tested. However, the overall effects are limited, with a maximal yield increase by only 7.0% and a maximal increase of the grain Zn density from 19.4 to 27.0 mg/kg, which is far below the target biofortification value of 40-50 mg/kg. Unfortunately, there was a negative side effect, which decreased Fe and Mn concentrations and the Fe bioavailability. Notably, grain yields and Zn concentrations were significantly increased by drone-based foliar Zn sprayings from 7.5 to 8.6~8.8 t/ha by 12.0-17.3% and from 33.5 to 41.9~43.6 mg/kg by 25.1~30.1%, respectively, indicating a double-win in yield and nutrition. A spraying of ZnSO4·7H2O increased grain Zn concentrations and accumulation more so than ZnO, indicating the importance of chemical Zn forms in determining the effectiveness of foliar spraying. Moreover, foliar Zn sprayings simultaneously increased grain concentrations and accumulation of Fe, Mn and Cu, demonstrating multiple benefits. There were positive correlations between Zn and Fe, Mn or Cu, indicating synergistic but not antagonistic interactions. Compared to micronutrients, concentrations of grain macro- and medium nutrients (N, P, K, Ca, Mg) were less affected. Thus, a double-win in grain yields and micronutrient (particulaly for Zn) nutrition could be effectively achieved through appropriate soil fertilization and foliar Zn spraying. These results provide a better understanding of the yield-nutrition relationship among wheat grain yields, Zn and other nutrient elements for a better integrated manipulation to achieve a win-win situation in yield and nutrition.