The EU has developed ambitious policies and regulations to halt biodiversity loss resulting from intensive use of forests and land and climate change. Reversing the decline of biodiversity requires safeguarding existing biodiversity and fostering the adaptive capacity and resilience of the ecosystem. SafeNet relies on a portfolio of complementary tools to develop strategies and solutions to protect and foster biodiversity, while considering the need to manage forests for climate change mitigation, wood and ecosystem service provisioning. SafeNet integrates cutting-edge methods in biodiversity monitoring and mathematical modelling with massive remote sensing and species datasets to better understand the climate change induced shifts in the distributions and migration of genes, species, communities, ecosystems under different climate and forest and land use scenarios. This will allow the prioritization and implementation of anticipatory conservation and management measures, including the protection of corridors among the network of primary and old-growth and other ecologically valuable forests. SafeNet implements a multi-actor approach and engages key stakeholders, including policymakers, forest practitioners, regional and national authorities, certification bodies, and forest-value chain stakeholders, in regional Living Labs developed in case study areas covering four biomes across Europe, and a European level Policy Lab. Stakeholders will co-create solutions with researchers to develop sustainable strategies for real landscapes and innovate EU-level strategies and policies to reconcile conservation goals. Methodologies and scientific advances developed by SafeNet, as well as the transdisciplinary team’s expertise in mathematical biology, remote sensing, forest economy and ecology, environmental conflict management, policy analysis and science-policy interaction, and stakeholder engagement and dissemination-outreach, ensure the success of SafeNet and its impact.