Global freshwater resources are vital to humanity and Earth’s ecosystems, yet about one third of the global population is affected by water scarcity for at least one month per year. In these areas, the overuse of freshwater resources can lead to the threat of depletion, marking them as the global “water scarcity hotspots”. This study combines outputs from a global hydrological model (PCR-GLOBWB 2) with an extensive literature search to provide a comprehensive intercomparison of the key Drivers, Pressures, States, Impacts and Responses (DPSIR) that shape the water gap between water demand and availability at the most important water scarcity hotspots worldwide. Hydroclimatic change, population growth, and water use for the industrial, municipal and agricultural sectors are the most important driving and pressuring forces on the water gap, affecting both water quality and quantity. These Drivers and Pressures have been showing increasing trends at all hotspots, which is concerning for the future development of the water gap. Additionally, we identify and characterize seven clusters of hotspots based on shared DPSIR patterns, revealing their common mechanisms. Our work highlights the diversity of water scarcity related issues at hotspots, especially the variety of impacts involved and governmental responses in place. The results of our DPSIR analysis provide valuable insights for building causal networks representing water gap dynamics at the hotspots. They form a foundation for conceptual models that illuminate human-water interactions, trade-offs, and synergies at the hotspots, while guiding policymakers in addressing the multifaceted challenge of closing the water gap.