Study Region Karachi, the largest metropolitan and economic hub of Pakistan, is located along the Arabian Sea in a semi-arid climate zone. Study Focus This study evaluates the current status and future risks of groundwater depletion and seawater intrusion in Karachi using numerical modeling. The GMS MODFLOW model was employed to simulate groundwater flow, while MT3D and SEAWAT were used to assess salinity intrusion. Historical data from multilevel observation wells, rainfall, extraction rates, and land use changes were incorporated to develop and calibrate the model. Four scenarios were tested: (1) status quo, (2) reduced recharge, (3) increased extraction, and (4) a combined stress scenario. These scenarios aimed to reflect plausible future conditions driven by climatic variability and anthropogenic stressors. New Hydrological Insights Results show an annual groundwater decline of 0.5-1.0 m, with current seawater intrusion reaching 6.41 km inland. Under Scenario S1 (status quo), levels drop 5.52 m by 2043, with intrusion advancing to 8.10 km at Port Qasim and 8.90 km at Manora Island. Scenario S2 (75% recharge reduction) causes 6.6 m drawdowns and intrusion up to 10.67 km, while Scenario S3 (100% extraction increase) yields similar declines, pushing intrusion to 11.56 km. The extreme Scenario S4 (combined stress) shows 8.52 m declines with intrusion extending 17.78 km, threatening key urban and industrial zones. Integrated recharge, regulated pumping, and monitoring are urgently needed.