The CATALYSE project envisions fostering climate-neutral cities by advancing beyond fragmented experimentation towards mission-oriented policies that are deeply embedded in local contexts. Its core vision is to empower Knowledge Institutions (KI) as transformative hubs within mission-oriented innovation ecosystems. By strengthening the roles of KIs as trusted actors, CATALYSE aims to connect diverse stakeholders, scale social innovations, and enhance collaboration across Europe. The project seeks to create inclusive problem-solution spaces in 4 pilot cities (Leipzig, Manchester, Rotterdam and Vienna) that bridge local needs with global challenges, driving sustainable, socially innovative, and democratically legitimized transitions toward net-zero cities. Through this vision, CATALYSE addresses critical challenges in translating EU Cities Mission goals into localized actions, ensuring that cities can successfully navigate and lead their climate-neutral transformations.