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In general, the sustainability of the water supply system is indicative of an adaptive operational approach, wherein the decision-maker adjusts the system's performance based on the availability of water resources in a given time frame. In light of this, a novel framework is proposed in this study to evaluate sustainability, including three key indicators: resilience, reliability, and vulnerability. To address stressors that may lead to system failure, a multisectoral water allocation optimization is undertaken. In order to account for the future implications of climate change on the hydrological cycle, a simulation step, is incorporated, utilizing the Soil and Water Assessment Tool (SWAT) under various emission scenarios (RCP4.5 and RCP8.5), prior to integrating the streamflow data into our proposed optimal framework. To calibrate and validate historical data (2014–2019) and simulate future streamflow patterns (2025–2085), the Sistan Basin, located in an arid region of Iran, is analyzed as a case study. In light of the anticipated adverse impacts on the water supply system, certain adaptation measures, such as demand shrinkage scenarios, are considered to further appraise the proposed framework. Based on the final output, it is evident that the agricultural and industrial sectors, being the primary water consumers, are more susceptible to negative impacts resulting from the reduction in system sustainability. This susceptibility is primarily attributed to their highest vulnerability and comparatively lower reliability. [ABSTRACT FROM AUTHOR]