With the advent of the Fourth Industrial Revolution, the role of entrepreneurs has become more crucial than ever. As a result, an open innovation model is suggested here that can promote serial entrepreneurs by answering the following question: "How does the serial entrepreneur in open innovation conditions continuously identify business opportunities?" This question is answered through an in-depth case study of Medison from 1985 to 2016, as Medison is not only a representative Korean medical device company, but is also a representative example of serial entrepreneurship in Korea. First, we examined the diverse open innovation channels, such as spin-offs, venture investment, and joint venture, used by Medison before it was merged with Samsung. Second, we examined the open innovation serial entrepreneurs of Medison and then analyzed the direct serial entrepreneurs of Medison. Fourth, we built a causal loop model of Medison open innovation with emergence and complexity combined. Finally, a sustainable open innovation strategy and an approach to sustainable serial entrepreneurship was formulated. The foundation of this research is as follows. First, an open innovation strategy can be a strong motivator for serial entrepreneurs. Second, a balance between emergence and complexity is required to trigger sustainable serial entrepreneurs of open innovation.