This study analyzed the role of the Triple Helix and Quintuple Helix models in innovative ecosystems through an integrative literature review of publications indexed in the Clarivate Web of Science database. The research was based on the understanding that contemporary innovation depends on collaborative relationships among universities, industries, governments, society, and the environment, particularly in contexts characterized by digital transformation, sustainability, and regional development. Methodologically, the study was qualitative, descriptive, and exploratory, employing a Boolean search string applied to the Web of Science database. The initial search yielded 625 publications, which were subsequently reduced to 170 articles after applying open-access and publication-period filters (2021–2026). Following thematic screening, the selected articles were organized into three analytical categories: ecosystem governance and coordination; sustainability and socioecological transitions; and entrepreneurship, knowledge transfer, and innovative performance. The findings revealed that ecosystem governance constitutes a central element for institutional coordination and the strengthening of collaborative innovation networks. Furthermore, sustainability was found to broaden the analytical scope of helix models by incorporating social and environmental dimensions into innovation processes. In parallel, findings related to entrepreneurship and knowledge transfer demonstrated that innovative ecosystems rely on the articulation between scientific production, applied innovation, and institutional cooperation. The study concludes that the Triple Helix and Quintuple Helix models provide significant analytical capacity for understanding the dynamics of innovation, sustainability, and regional development within contemporary innovative ecosystems.