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The future resilience of water supply systems is unprecedentedly challenged by non-stationary processes, such as fast population growth and a changing climate. A thorough understanding of how these non-stationarities impact water supply resilience is vital to support sustainable decision making, particularly for large cities in arid and/or semi-arid regions. In this study, a novel modeling framework, which integrates hydrological processes and water management, was established over a representative water limited metropolitan area to evaluate the impacts of water availability and water demand on reservoir storage and water supply reliability. In this framework, climate change induced drought events were selected from statistically downscaled Coupled Model Intercomparison Project Phase 5 outputs under the Representative Concentration Pathway 83 scenario, while future water demand was estimated by the product of projected future population and per capita water use. Compared with the first half of the 21st century (2000-2049), reservoir storage and water supply reliability during the second half century (2050-2099) are projected to reduce by 16.1% and 14.2%, respectively. While both future multi-year droughts and population growth will lower water supply resilience, the uncertainty associated with future climate projection is larger than that associated with urbanization. To reduce the drought risks, a combination of mitigation strategies (e.g., additional conservation, integrating new water sources, and water use redistribution) was found to be the most efficient approach and can significantly improve water supply reliability by as much as 15.9%.