This study develops a three-dimensional heterogeneous numerical model to simulate the water inrush process and predict the water yield for mineral exploration in Yangzhuang Iron Mine in Anhui Province. To identify the hydrogeological parameters of the aquifer in the study area, the model was calibrated and validated using the observed heads through the integrated trial-and-error and automated techniques. Also, the sensitivity analysis of the model was performed to evaluate the uncertainty associated with the calibrated model. According to the mine construction plan at different mining levels of-500 m,-600 m, and-700 m, the calibrated model was then applied to predict the water yields dependent on the different mining levels. As indicated by the prediction results, the numerical simulation model can systematically describe the groundwater system in the mining area and determine the source of water inrush in this iron mine. In conclusion, numerical analyses carried out in this study can provide guidance to decision-makers in balancing the iron ore mining and mine dewatering in the future. This study develops a three-dimensional heterogeneous numerical model to simulate the water inrush process and predict the water yield for mineral exploration in Yangzhuang Iron Mine in Anhui Province. To identify the hydrogeological parameters of the aquifer in the study area, the model was calibrated and validated using the observed heads through the integrated trial-and-error and automated techniques. Also, the sensitivity analysis of the model was performed to evaluate the uncertainty associated with the calibrated model. According to the mine construction plan at different mining levels of-500 m, -600 m, and-700 m, the calibrated model was then applied to predict the water yield dependent on the different mining levels. As indicated by the prediction results, the numerical simulation model can systematically describe the groundwater system in the mining area and determine the source of water inrush in this iron mine. In conclusion, numerical analyzes carried out in this study can provide guidance to decision-makers in balancing the iron ore mining and mine dewatering in the future.