A groundwater resource characterisation and assessment model was developed for Nasia river sub-basin in the White Volta Basin, Ghana. The model is useful to policymakers for planning and sustainable management of groundwater resources in the basin for domestic and irrigation purposes. A conceptual model was constructed that characterized boundary conditions and hydrostratigraphy, and estimated recharge rates and hydraulic and storage parameters. From current understanding of the hydrogeological dynamics, three hydrostratigraphic layers were delineated. The conceptual model was converted to a three-dimensional steady-state groundwater flow model using MODFLOW. Recharge rates estimated from the base model indicate a minimum of 1.1% and maximum of 6.2% of the total rainfall. The hydraulic conductivity ranged between 0.20 and 15 m/day. Four possible scenarios were simulated: (1) increased population, (2) climate variations (reduced recharge), (3) increased abstraction for irrigation, and (4) worst-case scenario which is a combination of the first three scenarios. Results from scenarios 1 and 2 indicated that, under such conditions, the groundwater resources could be sustained and no significant effect on any of the water budget indicators was observed. For scenario 3, there was significant drop in hydraulic head in the central portions of the study area. The scenario 4 simulation indicated that there was significant reduction in groundwater levels and groundwater discharge into streams under these stressors. Such reduction can affect stream levels in the basin and, subsequently, the ecosystem. These findings are valid within the limits of uncertainty in the hydrogeological data that were used in this study.