Cardiovascular disease (CVD) prevention and management strategies are effective but poorly implemented, especially in urban and underserved communities that would benefit the most. Cities@Heart aims to develop, pilot, and evaluate strategies that will reduce both the burden of CVD and health inequalities. Building on the existing European Healthy Cities Network by partner World Health Organization (WHO), and work by the World Heart Federation, European Society of Cardiology, European Public Health Association and HL7 Europe, we will provide a solid infrastructure that embeds innovative health technology to ensure scalability and sustainability. Cities@Heart will focus on obesity, hypertension, dyslipidaemia and diabetes as key drivers of CVD that can leverage engagement and citizen empowerment. We will develop and deploy derivation and implementation pilots for CVD awareness, effective prevention, early detection, and optimal management at the urban level. The municipalities of Izmir (Turkey), Belfast (Northern Ireland), Łódź (Poland), Cork (Republic of Ireland), Udine (Italy), Birmingham (England) and Utrecht (Netherlands) have diverse communities with differing health inequalities, with a commitment and past experience to deploy multi-disciplinary health strategies. Together with citizen and industry co-creation, these cities will apply a structured, multi-sector methodology that includes: (1) city-level approaches to reduce the burden of CVD; (2) a digital ecosystem that will power the development of European health technology and economic growth, (3) integration of health policy and health economics to deliver cost-effective city-level solutions; and (4) sustainability at its core using an implementation framework that can apply across European cities. Cities@Heart will build connections and capacity across our broad array of stakeholders through a strong public-private partnership. Together, we will support the next generation of health technology to address critical barriers for optimal CVD care in Europe.