Many studies concerned with investigating the groundwater resources of the Nubian Sandstone Aquifer System (NSAS). However, these studies focused either only on the regional groundwater hydrodynamics of the aquifer, or on local-scale case studies without taking into account the regional boundary conditions of the whole system. This work was an attempt to develop a three-dimensional transient groundwater flow model for the NSAS that is based on GIS-Database integration. This approach was proposed to 1) define and calibrate the regional boundary conditions of the NSAS, 2) to simulate the groundwater management options for the different stressed areas within the aquifer, and 3) to predict the environmental impact of the present and future groundwater extraction schemes on the different exploitation sites. The calibration was carried out under the transient conditions using the trial and error method for the period 1960-2005 based on the availability and temporal distribution of the data. The calibrated regional model was used afterward for the development and integration of local-scale (refined) models for the Dakhla oasis, Lake Nasser, and the Tushka area, to consider local detailed data inputs and to give a deeper view on the local hydrodynamic changes. Based on the actual and full capacity planned extraction rates of the NSAS, five extraction scenarios were suggested in an attempt to investigate the most feasible groundwater management option in terms of the economic lifting depth in a prediction simulation until 2100. The results of simulating the present extraction rates of the NSAS showed that the free flowing phenomenon will disappear all over the modeled area and the average depth to groundwater will range from 5 m in the Bahariya oasis to 36 m (bgl) in the Kharga oasis at the end of the simulation. At this simulation time, a groundwater volume of 354 km³ will be extracted from the aquifer storage. The application of scenario 3 was found to be the optimal groundwater management option that meets the development ambitions and the proposed economic lifting depth, while scenario 5 resulted in a depth to groundwater values sink faraway beyond the 100-m (bgl) limit of the economic lifting depth in the Kufra oasis and the East Oweinat area. In the Dakhla oasis the simulation of scenario 1 showed that the depth to groundwater in all the cultivable areas will be less than 75 m (bgl) by 2100 and the annual change in the hydraulic head would be 0.57 m/y. On the other hand, it was concluded that scenario 3 is the allowable groundwater development option in the Dakhla oasis, while scenario 5 led to successive increase of the depth to groundwater to have values greatly exceeding 100 m and cover most of the oasis. Lake Nasser raised the groundwater level with an average of 25 m within a 25 km strip and recharged the NSAS with a volume of 281.5 km³ until 1998. The cumulative recharge from Lake Nasser and the Tushka lakes until 2005 was calculated to be about 9.66x1011 m³.