We present a risk triage framework to provide a computationally efficient assessment of spatial vulnerability to multiple human and environmental stressors. Our framework adopts a multi-sectoral approach which considers two group of stressors in human, managed, and natural systems. The climate-driven stressors explicitly characterize different hydrological and temperature extreme conditions (drought, flood, heat, etc.), while human-driven stressors represent a wide range of socioeconomic aspects, such as population demographics, economic development, energy production and infrastructure, water supply and use, and land use change, etc. Our initial effort assembles a vulnerability assessment under contemporary conditions, which will serve as a baseline against foresights into potential tipping points and instabilities. We account for several sources of uncertainties in vulnerability indicators derived from multiple data sources and across different time periods as well as spatial scales. The triage framework offers a unique ability to screen and/or combine multiple indicators and visualize their co-evolutions via a GIS-enabled interface. In particular, “hotspots” of spatial vulnerability can be identified across a variety of geographic scales (e.g. regions, states, counties, or river basins) and prioritized for further research. Our results can also help inform policy makers as they consider risk management strategies and decisions.