The destabilization of delta's worldwide due to climate change and human activities presents challenges in meeting the growing demands for freshwater and food. The Nile Delta in Egypt is a prime example of a vulnerable region facing various stressors. In order to preserve land and water resources, it is crucial to monitor the spatial and temporal changes in Land Use/Land Cover (LULC), shoreline, and Terrestrial Water Storage (TWS) in these vulnerable regions This study comprehensively investigates the dynamic changes in LULC and their associated water and soil responses in the Eastern Nile Delta under these combined impacts. To achieve this goal, a combination of remote sensing techniques utilizing Landsat (5, 8, and 9), and GRACE datasets, along with field observations and Geographic Information System (GIS) tools, was employed. Accordingly, shoreline changes show coastal erosion rates ranging from 5.28 to 34.92 m/year due to climate change-induced SLR, with continued inland movement predicted for the next 20 years. Moreover, the dynamic changes in urbanization and alterations in agricultural cover have considerable penalties for water demand. Analysis of GRACE data indicates a notable reduction in average TWS by 77.89 mm between 2002 and 2017, with an annual rate, estimated at −5.821 mm/year. Soil sampling in highly vulnerable areas confirms agricultural degradation attributed to elevated salinity levels, with EC values ranging from 3.60 to 190 ds/m. These finds provide valuable insights for stakeholders and policymakers, to make reliable strategies regarding water allocation, land use regulations, and climate change adaptation in the worldwide vulnerable deltas.