Each year, pollution claims thousands of lives across Europe, yet city administrations struggle with limited resources and the need to balance the multiple and uncertain effects of potential solutions. PUREPOLIS is set to transform urban health by pioneering advanced tools that empower policymakers to take high-impact action. At its core, PUREPOLIS drives data-driven, citizen-powered, and science-backed decision-making. A breakthrough Citizen Science Application (PR1) will enhance engagement and real-time monitoring. The Near Real-Time Pollution Source Apportionment tool (PR2) and Risk-based Health Impact Assessment framework coupling epidemiology and toxicology approaches (PR3) will precisely link exposure to 35 pollutants and their combination across air, noise, water, and soil to 10 critical health risks, including wellbeing. To maximize the efficiency of Zero Pollution Measures, PUREPOLIS will deploy cutting-edge analysis (PR6) to assess their effectiveness in terms of health, economic, and climate impacts, embracing a complexity perspective. These insights will feed into a Dynamic Abatement Strategies Toolbox (PR7), ensuring seamless policy integration into co-created, tailored comprehensive strategy for each of the two case studies in France and Spain, optimising co-benefits with multiple policy sectors. PUREPOLIS also pioneers a Vulnerability framework (PR4) and Behaviour framework (PR5) to drive behavioural changes for more successful interventions and foster equitable and sustainable solutions. Beyond core cities in France and Spain, a next-gen Digital Twin (PR8) and policy reports (PR9) will ensure replicability, scalability, and real-world impact across Europe. With nineteen partners from eight countries over thirty-six months, PUREPOLIS is an unprecedented step forward for healthier, more resilient cities. By fusing science, digital innovation, and citizen-driven action, PUREPOLIS sets a new gold standard for pollution mitigation in Europe.