PurposeThe paper aims to contributes on the debates about University Idea Incubation by investigating the role and the engagement of different University's stakeholders in the process of opportunity recognition in an entrepreneurship education program targeted at students with an interdisciplinary background.Design/methodology/approachThrough a longitudinal case study methodology, the Contamination Lab at University of Salento (Lecce, Italy), the learning approaches and the knowledge process to create an entrepreneurial awareness, mindset and capability in students with different educational background are presented.FindingsThe findings demonstrates the crucial role of stakeholders' engagement for business idea presentation, open innovation challenge, contamination workshop on specialized topics, enterprise projects are important vehicle for effective students' business ideas and innovative projects development in a multidisciplinary environment. The close interaction among students, academia, companies and institutions creates a favourable environment that enables opportunity identification, idea generation through a deep contamination of knowledge, skills and experiences.Research limitations/implicationsLimitations include the need to generalise the results even if this limitation is typical of the case study methodology. Other research is necessary for an in-depth analysis in deep of the other Contamination Lab in Italy and to derive the “invariance traits” of this environment according to the features of the local entrepreneurial ecosystems.Practical implicationsImplications for practices include recommendations for designing innovative programs where the interactions between University-Institutions-Industry are realized.Originality/valueA conceptual framework is proposed by defining all the entrepreneurial knowledge process and knowledge creation within the Contamination Lab, highlighting the contribution of the stakeholders in each phase and learning initiative of the program.