Groundwater resources are becoming increasingly scarce, especially in arid regions of western Kazakhstan. By 2070, the domestic and drinking water demands will increase from 640 to 901 thousand m3/day. This deficiency may be overcome by utilizing the Zhem Artesian Basin's Cretaceous Albian-Cenomanian aquifer complex. The hydrodynamic interactions between the 123 known aquifer segments and recharge zones of these promising, exploitable, high-quality groundwater sources are unclear. While MODFLOW is a nominal platform for groundwater flow assessment, which is usually used for the simulation of simple hydrological scenarios, in this study, integrating several different scales and functional modules over a GIS platform enabled delineation and the forecast of this multi-layer aquifer complex. The MODFLOW simulation assessed exploitable groundwater resources and reservoir interactions, enabling the establishment of a simultaneous operation to the Zhem aquifer complex and its neighboring reservoirs. The model suggests that the total exploitable groundwater resources may grow to 629.4 thousand m3/day during the next 50 years. The simultaneous drawdown model suggests a water level decrease of up to 80 m at the end of this period, which will cause a river flow reduction of approximately 6% of the average long-term river flow. Thus, the assessed exploitable groundwater resources will cover more than 70% of the future regional water demand. The mathematical model developed may be used for monitoring and forecasting groundwater head and water balance changes and may be applied to attain a more detailed groundwater resource transfer scheme with economic criteria.