This article explores how eco-innovation practices are integrated into different industrial ecosystems in different national and regional contexts, and the role of the quintuple helix model in this integration. The research examines the collaborative interaction of academia, industry, government, civil society, and the natural environment in fostering an integrated eco-innovation ecosystem. The findings underscore the central role of the Quintuple Helix framework in effectively managing eco-innovation, suggesting a comprehensive approach that integrates environmental and societal concerns into a dynamic system for sustainable progress. The study shows that an ecosystem-based approach, underpinned by the quintuple helix, facilitates the rapid exchange of knowledge and resources essential to overcoming eco-innovation challenges, such as high R&D expenditures and the complex integration of sustainable technologies. The quintuple helix model emerges as a strategic imperative for concerted action to achieve eco-efficiency and eco-effectiveness. The study employs an innovative methodological framework based on Quintuple Helix projections using the Eco-Innovation Index (Eco-IS) and highlights significant trends in the roles of academia, industry, government, civil society, and the natural environment in eco-innovation, with a particular focus on their contributions to eco-innovation leaders, average performers, and catching-up groups. The article describes the different roles and interdependencies of the actors within the ecosystem and urges a coherent, networked strategy for managing eco-innovation, which is crucial for sustainable and responsible growth. Acknowledging the issue of externalities that complicate eco-innovation management, the article posits that the quintuple helix framework can better address these challenges by enabling shared R&D investments and broad diffusion of innovations. This research contributes to the discourse on sustainable industrial development by proposing the quintuple helix as a transformative model for improving eco-innovation performance and fostering a culture of sustainability.