AQUACOSM-plus advances European mesocosm-based aquatic RI by integrating the leading mesocosm infrastructures into a coherent, interdisciplinary, and interoperable network covering all ecoregions of Europe. AQUACOSM-plus widens the user base by extending TA provision (> 13000 person-days), and strengthening the offered services, with 10 new partners, including a NGO and doubling of SMEs. We initiate actions to increase competence in mesocosm science in new EU member states (Hungary and Romania), and emphasize training of young scientists through summer schools covering various disciplines including effective science communication. AQUACOSM-plus develops near-real-time Open Data flows and improved metadata, thus promoting Open Mesocosm Science in collaboration with leading EU-supported initiatives in the EOSC and fosters wider sharing of information, knowledge, and technologies across fields and between academia, industry, and policy makers/advisers. AQUACOSM-plus develops new technological capabilities for mesocosm research, to effectively execute scenario-testing for Climate Change -related pressures on aquatic systems from upstream fresh waters to the sea. These developments include mobile large-scale mesocosm approaches, leading-edge imaging technologies, and affordable methods to obtain high-frequency data on community change and greenhouse gas fluxes in mesocosm settings. AQUACOSM-plus will progress beyond current achievements by actively pursuing RI-RI collaboration with European environmental RIs (LTER, ICOS, DANUBIUS, JERICO) at all project activity levels (NA, JRA, TA). Multidisciplinary joint research, combining observational data and modelling approaches with targeted mesocosm experiments, is a key step towards successfully tackling current and future Grand Challenges. This involves shared capacity building via symposia, expert summits, and open workshops, with the aim of co-designing future aquatic research actions and their RI demands.