The proactive sustainable management of scarce water across vulnerable agricultural areas of South Europe is a timely issue of major importance, especially under the recent challenges affecting complex water systems. The Basin District of Thessaly, Greece’s driest rural region, has a long history of multiple issues of an environmental, planning, economic or administrative nature, as well as a history of conflict. For the first time, the region’s key-stakeholders, including scientists and policymakers, participated in tactical meetings during the 19-month project “Water For Tomorrow”. The goal was to establish a common and holistic understanding of the problems, assess the lessons learned from the failures of the past and co-develop a list of policy recommendations, placing them in the broader context of sustainability. These refer to enhanced and transparent information, data, accountability, cooperation/communication among authorities and stakeholders, capacity building, new technologies and modernization of current practices, reasonable demand and supply management, flexible renewable energy portfolios and circular approaches, among others. This work has significant implications for the integrated water resources management of similar south-European cases, including the Third-Cycle of the River Basin Management Plans and the International Sustainability Agendas.