This paper introduces euPOLIS; an EU funded project, which emphasize on the appropriate development of urban ecosystems in a way that enhance Public Health (PH) and Well-Being (WB) without significant Life-Cycle costs. Such an approach has has the potential to regenerate urban ecosystems addressing multiple challenges, such as low environmental quality, fragmentation and low biodiversity in public spaces, water-stressed resources, undervalued use of space in deprived areas resulting in an improved urban livability. The proposed methodology is expected to improve people’s quality of life, providing them with pleasant socializing open areas that stimulate social exchange while monitoring the impact of all those interventions to PH and WB of citizens. The euPOLIS suggested solutions will be demonstrated in 4 European cities: Belgrade, Lodz, Piraeus and Gladsaxe.