Under rapidly growing water demand and the potential prolonged drought due to climate changes, a long-term sustainable water supply must be assured. This study develops a generally applicable decision support system (DSS) tool as an aid in the planning of long-term water supply. The model incorporates multiple water sources (ex, ground water, surface water, natural and artificial recharge), users (ex, municipal, agricultural, industrial, and natural evapotranspiration), and water qualities (ex, raw water from sources, treated potable and reclaimed water). In addition, sustainability indicators are developed and applied in general water system to quantify future water supply sustainability based on multiple scenarios (representing future conditions of water supply and demand) utilizing the developed DSS model. The DSS model and sustainability quantification indices will support the public and stakeholders in decision making process through the scenario analysis representing potential future water conditions. The application of the DSS model will be demonstrated through a case study on the regional water supply system in Tucson, AZ.