The challenge of providing the inhabitants of European cities with affordable, safe, and nutritious food is both urgent and complex. Moreover, the health and wellbeing of EU citizens and consumers are directly affected by the way cities and regions themselves are shaping a sustainable food environment. Research and (open) innovation co-created with citizens are part of broader city-region food system approaches. Such initiatives stimulate the development of cities as innovative food hubs. Nevertheless, there are barriers to the application and demonstration of systemic food-related innovative approaches due to the diversity of European cities and regions that are not well understood, leading to market failure in the uptake of promising research results and innovation in cities. Demonstration and first application in the market of innovative solutions, co-created with citizen and cities with the involvement of public authorities, economic actors and non-profit organisations, could be one way to support sustainable food security in cities.