This chapter deals with the genesis of an urban cultural and creative cluster (CCC) as a collective system of cultural and creative entrepreneurs and very small companies. Beginning with a longitudinal case study of the trajectory of a CCC, the purpose is to address the analysis framework of the clustering process and to identify the keys actors in the cluster life cycle. The methodology is based on a 6-year qualitative study of the French “Quartier de la création” in Nantes. The findings confirm the prevailing view of the CCC as a dynamic organization. It shows distinct stages, with specific key actors and governance practices. It reveals difficulties in shaping the roles of the support organization, the interactions with the small firms, and the collective competencies to build amongst the cultural and creative entrepreneurs. The governance mechanisms and cluster practices of some localized groupings of cultural entrepreneurs and very small creative enterprises require balancing institutional and entrepreneurial approaches, which results in hybrid cluster practices based on ambidextrous management mechanisms.