Aquifer depletion due to excessive groundwater use is a global issue that should be adequately addressed to avert the associated severe consequences. Thus, the MODFLOW-USG model was integrated with the walrus optimizer (WO) to form a novel simulation–optimization (S–O) framework for promoting sustainable groundwater management, particularly in water-scarce areas. The MODFLOW-USG/WO framework was applied to the Egyptian region, namely Wadi El-Natrun, which is experiencing declining groundwater levels. The MODFLOW-USG model was calibrated, leading to high accuracy in simulating groundwater levels with a correlation coefficient of ~1. Besides, the existing groundwater extraction rate was about 0.227 million m3/day (current situation), resulting from flow budget analysis. Two scenarios were examined to simulate the variation in groundwater levels by increasing the current situation by 20% (scenario No. I) and 40% (scenario No. II). Both scenarios predicted significant groundwater level declines by 2030, especially in the basin’s southwest. The research study then combined MODFLOW-USG with WO, outperforming other methods, while testing a hypothetical aquifer problem. Using this integrated S–O framework, extraction rates of 0.259 and 0.291 million m3/day, representing 114% and 128% of the current situation, were obtained to guarantee median drawdown values across the basin, respectively. The suggested S–O approach developed in this research study has potential applications beyond the Wadi El-Natrun basin. It could be a valuable tool for managing groundwater resources efficiently in similar regions across the globe, contributing to the achievement of sustainable development goals (SDGs).