Freshwater comes from different sources unevenly distributed over time and space around the world and plays a key role in the planning of all social and economic sectors on a regional scale. In this context, a consistent framework for modeling regional water supply mix (WSmix) at a worldwide scale has already been developed for use in life cycle assessment (LCA). However, changes in water sources, driven by climate and socio-economic changes, will occur, affecting WSmix. This study aims to assess the need for a Prospective WSmix (P-WSmix) for implementation in LCA and water footprint studies as well as regional water management strategies. Environmental and socio-economic factors affecting future water supply are defined. Projections of the three main components of the P-WSmix (i.e., water sources mix (P-WOmix), technology evolutions, and associated electricity mix) are proposed for two water users (public water and irrigation), under three scenarios and time horizons until mid-21st century. For implementation of the P-WSmix in LCA, a P-WOmix database is provided for 74 countries on all continents as well as a prospective technological matrix and prospective electricity mixes. An illustrative case study shows the importance of including P-WSmix in LCI databases for the LCA of infrastructures or products with a long life span and tangible water use during use or end-of-life phase, through the example of a toilet flushing system. P-WSmix has an important added value in supporting regional adaptation strategies for the future water supply management.