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This chapter highlights the importance of strategically managing knowledge networks. Strategic management is defined as being aware of current knowledge networks, understanding current knowledge stocks, and identifying gaps. It also involves assessing the knowledge needs of business units and ensuring that those needs are addressed. The chapter also highlights the importance of having a vision of a healthy knowledge network.

Following the triple helix (TH) model and the way knowledge is transferred into the industry domain, this chapter aims to define features interface that should be implemented in order to facilitate the University–Industry (UI) relationship and thus encourage the spin-off creation.

In order to support this relationship, a new business model configuration of an entrepreneurial ecosystem is proposed, aiming at creating a sustainable environment, where business entities can grow. The field of the Governance of Entrepreneurial Ecosystems is also investigated in order to define a framework for launching, developing, and sustaining a company over time.

This chapter presents a case study developed within the University of Salento (Italy). It capitalizes results from three different research analyses, based on questionnaires and interviews with actors of the spin-off network (professors and researchers, graduating students, admin-tech staff of the Technology Transfer Office, spin-offs’ CEOs/Associates, and R&D managers of external companies) and on results coming from scientific publications and regional/national reports in the innovation context.

A research methodology based on semantic network analysis and sentiment analysis has been applied in order to identify which features an interface should implement in order to facilitate the UI relationship and encourage the spin-off creation.

To support the start-up overcoming the “death valley,” the creation of a link between the strategy used to transfer value to the market and the phase of innovation is proposed inside the business model configuration. Some aspects of a governance model of an entrepreneurial ecosystem were also presented in order to support the business evolution of a single business entity and assuring sustainability over time.

Given the numerous government initiatives in existence improving the transfer of knowledge to high-tech small- and medium-sized enterprises (HTSMEs) appears to be a highly relevant topic (Bougrain & Haudeville, 2002). For example, governments provide subsidies, give training, found knowledge-brokering institutes, websites, and support collaboration between HTSMEs and research institutes (Jetter, Kraaijenbrink, Schröder, & Wijnhoven, 2005). Although government initiatives are undoubtedly helpful in supporting the transfer of knowledge into HTSMEs, they are not the only way to support them. An alternative way to support HTSMEs is by providing them with the Methods and Software Tools (MSTs) they need to identify, acquire, and utilize external knowledge. This process of identifying, acquiring, and utilizing knowledge from their environment is termed external knowledge integration (EKI) in this chapter.