The European Union is significantly investing in the Green Deal that introduces measures to guide Member States to face sustainability and health challenges, especially employing Nature-Based Solutions (NBS) in urban contexts. National governments need to develop appropriate strategies to coordinate local projects, face multiple challenges, and maximize NBS effectiveness. This paper aims to introduce a replicable methodology to integrate NBS into a multi-scale planning process to maximize their cost-benefits. Using Italy as a case study, we mapped three environmental challenges nationwide related to climate change and air pollution, identifying spatial groups of their co-occurrences. These groups serve as functional areas where 24 NBS were ranked for their ecosystem services supply and land cover. The results show eight different spatial groups, with 6% of the national territory showing no challenge, with 42% showing multiple challenges combined simultaneously. Seven NBS were high-performing in all groups: five implementable in permeable land covers (urban forests, infiltration basins, green corridors, large parks, heritage gardens), and two in impervious ones (intensive, semi-intensive green roofs). This work provides a strategic vision at the national scale to quantify and orient budget allocation, while on a municipal scale, the NBS ranking acts as a guideline for specific planning activities based on local issues.