Climate change in combination with increased anthropogenic activities will affect coastal groundwater systems throughout the world. In this paper, we focus on a coastal groundwater system that is already threatened by a relatively high seawater level: the low-lying Dutch Delta. Nearly one third of the Netherlands lies below mean sea level, and the land surface is still subsiding up to 1 m per century. This densely populated delta region, where fresh groundwater resources are used intensively for domestic, agricultural, and industrial purposes, can serve as a laboratory case for other low-lying delta areas throughout the world. Our findings on hydrogeological effects can be scaled up since the problems the Dutch face now will very likely be the problems encountered in other delta areas in the future. We calculated the possible impacts of future sea level rise, land subsidence, changes in recharge, autonomous salinization, and the effects of two mitigation countermeasures with a three-dimensional numerical model for variable density groundwater flow and coupled solute transport. We considered the effects on hydraulic heads, seepage fluxes, salt loads to surface waters, and changes in fresh groundwater resources as a function of time and for seven scenarios. Our numerical modeling results show that the impact of sea level rise is limited to areas within 10 km of the coastline and main rivers because the increased head in the groundwater system at the coast can easily be produced though the highly permeable Holocene confining layer. Along the southwest coast of the Netherlands, salt loads will double in some parts of the deep and large polders by the year 2100 A.D. due to sea level rise. More inland, ongoing land subsidence will cause hydraulic heads and phreatic water levels to drop, which may result in damage to dikes, infrastructure, and urban areas. In the deep polders more inland, autonomous upconing of deeper and more saline groundwater will be responsible for increasing salt loads. The future increase of salt loads will cause salinization of surface waters and shallow groundwater and put the total volumes of fresh groundwater volumes for drinking water supply, agricultural purposes, industry, and ecosystems under pressure.