Groundwater resources constitute approximately 30% of the world’s freshwater supply, providing essential support for agricultural production, industrial development, and domestic needs for billions of people globally. With increasing pressures from population growth, climate change, and intensifying land use, sophisticated groundwater modeling approaches have become critical tools for sustainable water resource management in vulnerable regions worldwide. This comprehensive review critically examines groundwater modeling approaches in the Nile Delta, Egypt, where intensive anthropogenic activities and climate change threaten this vital resource. The study evaluates methodological evolution from simple analytical techniques to sophisticated three-dimensional numerical models, highlighting advances in process representation across seawater intrusion, contaminant transport, and management optimization domains. Despite significant progress, persistent challenges include inadequate spatiotemporal monitoring networks, limited data integration, and insufficient representation of human–natural system interactions. Seawater intrusion modeling reveals coastal intrusion extending 60–80 km inland, with projections suggesting 5–15 km additional intrusion by 2100. Contaminant transport studies document agricultural pollutants affecting 30% of shallow aquifers, while management models demonstrate spatially variable sustainable extraction limits. The review identifies critical research gaps, including inadequate uncertainty quantification, limited implementation pathway analysis, and insufficient integration of socioeconomic factors with physical models. Future research directions should prioritize integrated socio-hydrological frameworks, enhanced stakeholder engagement, and robust decision-making approaches under deep uncertainty. By synthesizing methodological advances, persistent limitations, and promising research directions, this review provides guidance for sustainable groundwater management in the Nile Delta and comparable deltaic systems worldwide facing similar challenges from climate change, population growth, and intensive resource exploitation.