In this paper, we build a theoretical framework to better understand the polycentric governance of global socio-ecological challenges through the lenses of meso-institutional analysis. Climate change, deforestation, pollinator decline, and loss of soil fertility are examples of complex socio-ecological challenges caused by anthropic pressures at a global scale. These challenges result in intractable social dilemmas and absent or weak macro-institutions, posing questions on how subsidiary mechanisms of coordination can be adopted in a polycentric governance approach. Building on the meso-institutional framework and socio-ecological systems framework, we investigate the emergence and establishment of multi-stakeholder partnerships (MSPs), where businesses, governments, and civil society organizations try to address global challenges. Recognizing meso-institutional functions in MSPs allowed us to expand our theorizing of the polycentric governance of global socio-ecological challenges, looking at nested, interrelated, and multi-layered relations between multiple actors and organizations.