This chapter provides an overview of the geological and hydrological characteristics of Viet Nam’s Mekong Delta, as well as of the main anthropogenic drivers of change. We also present the temperature and precipitation changes over the past four decades, and assess future climate change according to different global climate scenarios, applying statistical and dynamic downscaling methods. Increasing temperatures are recorded at all stations in the Delta, with an average warming trend of ~0.2°C/decade, while precipitation changes are more contrasted. By mid-century, temperature is projected to increase by 1.3°C to 1.8°C and precipitation by 15% to 20%, under climate scenarios RCP4.5 and RCP8.5 respectively. By the end of the century, the temperature increase could reach 1.7°C to 3.7°C, and the precipitation increase 15% to 25%, depending on the global climate scenario. Climate change is not the only threat to the Delta’s future: human activities in the delta or upstream have strong impacts on hydrology and sedimentology and may exacerbate climate change impacts, or in some cases pose an even greater threat in the short- to midterm. Sediment trapping by upstream dams and excessive fluvial sand mining are the main drivers of enhanced saline water intrusions, while ground-water over-extractions also drive high subsidence rates, and hence rapid relative sea-level rise. Adaptation measures implemented up to now may be effective in terms of aquaculture and agricultural production, but are not sustainable from a social, economic, or environmental point of view. Therefore, a holistic approach is required to deal with future climate change and anthropogenic pressures, and to develop sustainable agriculture and aquaculture in the Delta.