This paper explores the transition of cities toward circular economy models introducing the case study of Genoa, Italy. The research explains the C-City strategic framework, designed to guide urban systems from a linear to a circular paradigm by integrating four pillars: Processes, Actors, Supply Chains, and Territory. The framework emphasizes the transformation of cities, embedding circularity across all stages of the value chain, moving beyond the most common milestone of waste management. To validate the applicability of the framework, the research implemented the model starting from the food supply chain, a sector with significant environmental and socio-economic impact. The study outlines a process-based approach—Design, Long Use, and Reuse—combined with stakeholder engagement and multi-scale governance. Findings highlight the importance of participatory strategies, adaptive planning, and cross-sectoral synergies for effective circular transition. The Genoa case demonstrates that cities can serve as experimental platforms for circular innovation, despite challenges related to governance tools and economic sustainability. The research contributes a scalable and adaptable model for other urban contexts, fostering resilience and inclusivity in long-term sustainability agendas.