This paper explores quadruple helix ecosystems, cultural hubs, and living labs as models for transformative partnerships for higher education institutions (HEIs) as they move towards more open, co-operative, and co-creative research and innovation formats for public good. The transition of HEIs from mode 2 to mode 3 institutions prompts a cultural shift in HEIs that involves ongoing reimagination and reconfiguration. Here, the paper introduces and connects the quadruple helix ecosystem, living labs, and public good as a way for HEIs to revitalise themselves and their societal role. Following this, the model of cultural hubs is put forward as a way for partners to meet in the middle to co-create for, in, and with the world. Here, the Horizon Europe EPIC-WE research and innovation project serves as a guiding example with its specific emphasis on co-operative research-making, culture-making, and innovation-making between higher education institutions (HEI), creative industries (CI), cultural heritage institutions (CHI), and youth citizens (YC). Within EPIC-WE, cultural hubs are positioned as having the potential to act as cross-sector, transdisciplinary mediators that support the quadruple helix partners in moving towards transformative partnerships and empowered participation for public good(s) together.