Knowledge-driven economies rely on innovation ecosystems and solutions that leverage digital infrastructure and viable governance supported by collaborative openness among institutions. This study aims to examine the effect of collaborative institutional openness, multi-level governance alignment, and digital civic infrastructure readiness on socially embedded knowledge spillover and triple helix trust density, and resulting outcomes on sustainable innovation performance and societal knowledge value realisation. Additionally, the study examines the moderating role of mission-oriented entrepreneurial orientation behavior for mission-oriented innovation. Implementing collaborative institutional openness, multi-level governance alignment, and digital civic infrastructure readiness enhances socially embedded knowledge spillover and thereby increases triple helix trust density. The two sequential methods help improve sustainable innovation performance and the realisation of societal knowledge value, underscoring the importance of trust-based relational architectures for innovation systems. Intriguingly, mission-oriented entrepreneurial orientation is negatively associated with the relationship connectedness of socially embedded knowledge spillover–triple helix trust density. If a collaborator focuses solely on a shared objective, it can be challenging to build trust with them. The research explains how structural, digital, and behavioral enablers impact sustainable innovation. Innovation ecosystems need to be open, ready for digital technology, trust-based, capable of changing their mission, and governed reflexively.