The Borena basin is located in southern Ethiopia, in a semi-arid climate, on the eastern shoulder of the south Main Ethiopian Rift (MER). The study area covers 18,000 km2 and is characterized by a lack of perennial surface waters that can be used for domestic and agricultural purpose. As a result, groundwater, which occurs in complex volcanic settings, is the only source for water supply in the study area. This work is focused on the basaltic aquifers, which are intensely fractured, resulting in strong connectivity within the system. All available data (geology, hydraulic head, hydraulic parameters, well inventory and discharge, etc.) were compiled in a GIS database. The overall objective of this work is the assessment of groundwater potential, its spatial distribution and factors controlling its movement using numerical groundwater modeling to enhance groundwater management and use in the Borena basin. The modeling task was conducted at two scales: (i) regional scale; (ii) wellfields scale. The regional steady state model was calibrated using the Pilot points approach, highlighting a strongly heterogeneous system. A significant result of the regional model consisted of estimating the water balance of the whole system. The total inflow to the basin amounts to 542 × 106 m3/year, of which 367 × 106 m3/year are provided by superficial recharge. Groundwater resources are exploited with 7 wellfields. Exploitation of the wellfields was optimized based on the Sustainable Yield concept, which reserves a fraction of natural recharge for the benefit of the environment (surface waters, ecosystems). Each wellfield was extracted from the regional model, refined and used to simulate and optimize pumping scenarios, with the objective of maximizing discharge rates and avoiding over-exploitation of the groundwater. The optimized abstraction at all wellfields amounts to 121 × 106 m3/year, which represents 33% of the natural recharge and fully agrees with the sustainable yield concept.