Due to climate change, drought, and earthquakes, drinking supplies in the western U.S. and similar climatic regions globally will become strained, especially in densely populated urban areas, such as the City of Los Angeles (City). In response, the Los Angeles Department of Water and Power committed at least $6 billion to invest in Pure Water Los Angeles, also known as Operation Next. The initiative would treat wastewater to create a new local, sustainable, and reliable source of over 250,000 acre-feet of drinking water per year. By developing the Operation NEXT Resilience Analysis Model and analyzing about 100,000 scenarios, the researchers found that Operation NEXT would be a strategic investment to address immediate water supply challenges and offer long-term economic and water security benefits. Operation NEXT would: 1) offer substantial regional economic benefits; 2) significantly bolster local water supply resilience; 3) improve resilience to uncertain water imports; and 4) significantly reduce earthquake-driven water shortages. Because climate uncertainty will be the largest driver of the City's water shortage, the project should be designed to be adaptable. This analysis can inform broader planning efforts both in the U.S. and beyond.