Selecting representative groundwater monitoring wells in polluted areas is crucial to comprehensively assess groundwater pollution, thereby ensuring effective groundwater remediation. However, numerous factors can affect the effectiveness of groundwater monitoring well network optimizations. A local sensitivity analysis method was used in this study to analyze the hydrogeological parameters of a simulation groundwater solute transport model. The results showed a strong effect of longitudinal dispersion and transverse dispersion on the output results of the simulation model, and a good fit between the backpropagation neural network (BPNN)-based alternative model’s results and those obtained using the solute transport simulation model, accurately reflecting the input and output relationship of the simulation model. The optimized groundwater monitoring layout scheme consisted of four groundwater monitoring wells, namely no. 7, no. 16, no. 23, and no. 24. These wells resulted in a groundwater fluoride pollution rate of 98.44%, which was substantially higher than that obtained using the random layout scheme. In addition, statistical analysis of the fluoride groundwater pollution results obtained using the Monte Carlo random simulation highlighted continuous and high groundwater fluoride levels in the second and third pollution sources and their downstream groundwater. Therefore, more attention should be devoted to these sources to ensure the effective remediation of groundwater pollution in the study area.