Under the knowledge economy and digital technology-driven globalization, urban innovation ecosystems (UIEs) have transitioned from single-actor dominance to multi-stakeholder collaboration, making their development a core strategy for regional advancement. This study systematically examines the roles and mechanisms of “Eds and Meds” as anchor institutions in UIEs through the lens of multi-helix theoretical frameworks. By conducting a comparative analysis of global archetypes, such as the Texas Medical Center (U.S.), and Chinese cases like the Zhangjiang Biopharmaceutical Cluster and Jinan International Medical Center, this research uncovers how “Eds and Meds” function through knowledge production, institutional translation, spatial restructuring, and ecological transition mechanisms, systematically driving the dynamic evolution of urban innovation ecosystems. Key findings highlight that these anchor institutions not only orchestrate innovation but also serve as critical intermediaries bridging governments, industries, citizens, and natural environments, with their synergistic capacities fundamentally shaping the resilience and sustainability of UIEs.