Water scarcity, water quality degradation and the loss of freshwater biodiversity are critical environmental challenges worldwide, which have primarily been driven by a significant increase in water withdrawals during the last century. In the coming decades, climate and societal changes are projected to further exacerbate these challenges in many regions around the world. As such, defining a safe operating space (SOS) for water resources in a changing climate and society is urgently needed to ensure a sufficient and reliable supply of water of a quality acceptable for human activity and natural ecosystems. However, defining the SOS for the entire water resources system at spatial scales relevant to decision-making and its projections into the future requires going beyond state-of-the-art water system modelling toward a holistic and participatory assessment framework that includes data gathering, integrated modelling, and working with relevant stakeholders. SOS-Water aims to create the foundation for this framework. It will co-create future scenarios and management pathways with stakeholders in five case studies in Europe and abroad. It will advance water system models and link them with impact models of ecosystem services and biodiversity, to create a novel integrated water modelling system. This integrated water modelling system will be benchmarked against a wide range of state-of-the-art Earth observations and will be used to calculate selected indicators covering all dimensions of water resources systems, to ultimately design a multi-dimensional SOS of policies and water management pathways evaluated across a broad set of scenarios. The results of SOS-Water will help improving the understanding of water resources availability and streamline water planning and management at local to regional levels and beyond, such that the allocation of water among societies, economies, and ecosystems will be economically efficient, socially fair, and resilient to shocks.