Sustainable groundwater resources are a critical issue for national development in developing countries like Egypt, which is characterized by a semi-arid to arid climate and low per capita share of fresh water as a result of progressive population increase and especially after the construction of the Great Ethiopian Renaissance Dam. It is mandatory to adopt and modify methods suitable for preserving and efficient use of available water resources. The Eocene carbonate aquifer in the desert area under study (West El-Minia, Mid-Upper Egypt) is partially renewable; its sustainable development in irrigation is explored in this work. The (recharge–withdraw–exploit) regimes have been optimized by keeping the well abstraction below the fraction of renewable recharge and maximizing the exploit by selecting low water -consuming crops of high economic value. A novel approach is introduced in this work by integrating isotope hydrology techniques with numerical modeling; environmental isotopes (18O and D) contents of 62 groundwater samples have been used to determine and map the contribution of recent recharge in the study area (from 10 to 95%) and to constrain the acceptable reduction in hydraulic head allowed under an optimized withdraw and usage regime. Different scenarios were proposed by changing (rate of pumping, number of wells, wells distribution and irrigated crops) and simulating aquifer behavior to achieve the sustainable yield goals and the best plan for groundwater management in the study area.Graphical abstract