Water demands and stresses in the Vietnam Mekong Delta (VMD) are of high concern for the coming decade. System dynamics modeling (SDM) can be used to understand the impacts of the changes on water resources at a regional scale. SDM framework was applied to assess the impacts of land use changes and climate on surface water resource in the VMD. The developed model was modified from a global-scale model and added in-situ specific variables to model the conditions of the VMD using historical data during 1986–2005, and future projections to 2050 under two Representative Concentration Pathways scenarios (RCP4.5 and RCP8.5). Projected changes in land use and population were based on the most recent governmental resolution to support adaptation and the national plans. Temperature and rainfall changes cause the increase in water stress; however, it could be mitigated by shifting from three to two crops of rice each year. Water stress differs from place to place, such as in freshwater and brackish coastal zones. Water stress is most strongly affected by changed temperature, rather than rainfall. The developed system dynamics model and framework can be effectively applied in the VMD to support decision-making about sustainable water use for paddy rice.