Stakeholders and their dynamics are often neglected in innovation system literature. The importance of the bioeconomy is growing due to its implications for addressing environmental challenges, shaping economic decisions, markets, and sustainable development. This paper analyses stakeholders’ dynamics for knowledge creation and innovation to transit from unsustainable practices to the sustainable use of biological resources—the bioeconomy. The originality of this paper is the creation of an analytical framework to characterise the interactions of stakeholders and how these interactions reshape innovation systems to create a new narrative and knowledge-base platform for innovation. Using a qualitative approach, data were collected through surveys between 2022 and 2024. We explored the dynamics of 29 stakeholders involved and collaborating in R&D activities from the biotechnology sector in Caldas, Colombia. Our findings show that dynamics towards the bioeconomy are occurring only at the discursive level. Stakeholders carry out research activities to generate income rather than for innovative purposes, overlooking informal interactions that create novel ideas that could translate into solutions, services, and products. We conclude that the bioeconomy transition needs a systemic disequilibrium with a new institutional infrastructure that enables stakeholders, including civil society, to create a structural change for embracing innovation dynamics.