The frequency and intensity of climate and weather extremes associated with anthropogenic climate change are increasing and will challenge us in terms of adaptation strategies at the local level. The project “Climate Resilient Development Pathways in Metropolitan Regions of Europe (CARMINE)” bridges the local and regional scales by providing impact-based decision support services and multi-level climate governance supporting local adaptation, including both traditional and Nature-Based Solutions. CARMINE’s overarching goal is to help the metropolitan communities of Europe become more climate resilient, by co-producing knowledge-based tools, strategies, and plans for enhanced adaptation and mitigation actions in line with the Charter of the EU Mission on Adaptation to Climate Change by 2030. To achieve this goal, focusing on the 2030-2035 timeframe and with longer perspectives up to 2050, CARMINE proposes an interdisciplinary approach aiming at (1) co-creation and co-development of decision-support services and guidelines for enhanced resilience and adaptive capacity, including early warning and disaster risk management systems; (2) cooperating closely with local to regional communities (stakeholders and users), decision-, and policy-makers (local authorities) to co-develop cross-sectoral frameworks for adaptation and mitigation actions; (3) delivering science-based R&I roadmaps for multi-level climate governance supporting local adaptation assessments and plans. The CARMINE methodology will be implemented in eight selected Case Study Areas to demonstrate proof of concept and project methodology will be demonstrated through the digital replication of climate and socio-economic characteristics of each area. The co-created knowledge and transferable development pathways from CARMINE will be shared widely via project networks in order to drive adaptation in other metropolitan regions of Europe, and beyond.