Climate and anthropogenic changes are expected to reduce renewable groundwater resources and to increase the risks of water scarcity, particularly in arid regions. Understanding current and future risks of water scarcity is vital to make the right water management decision at the right time. This study aims to analyze the impact of both human and climate pressures on groundwater availability in an arid environment: the Regueb basin in Central Tunisia. An integrated approach was used and applied at a monthly time step over a reference period (1976-2005) and a future period (2036-2065). Groundwater resources were assessed using hydrogeological modeling. Irrigation water withdrawals were evaluated based on remote sensing and the CropWat model. Urban water use was estimated from population growth and specific monthly water consumption data. The resulting values were used to compute two indicators (water stress index, groundwater balance) to evaluate water scarcity risks at the 2050 horizon. To assess current and future climate forcing on water resources, three climate scenarios were generated based on simulations from Coupled Model Intercomparison Project Phase 5 (CMIP5) data. A business-as-usual and an adaptation scenario (optimal cropping scenario) were performed by varying the surface areas and the crops grown in the irrigated area. Results show that the average annual water use will increase by 3.8 to 16.4% under climate change only, whereas it will increase by 100% under the business-as-usual scenario. Under the optimal cropping scenario, total water demand will increase by 50%. Water stress index indicates that under the climate change only scenario, water demand should be satisfied by the 2050 horizon, while under the other two scenarios, severe water stress will occur by 2050. The developed framework in this paper aims to fit in arid and semiarid regions in order to evaluate groundwater stress and to assess the efficiency of adaptation strategies. It results in two major recommendations regarding changes in land use and the improvement of groundwater monitoring.