Interactions between firms, universities and other actors in the innovation system are essential for open innovation. Empirical literature on the relationship between open innovation strategies and firm performance in low-income countries however is less and heavily biased towards developed countries. This chapter examines the role of open innovation strategies on the innovation performance of firms in Ghana and Tanzania, and explores further the roles of university–industry collaborations and the participation of regional and global production networks on capability development of African firms. Based on primary data, our results show that open innovation strategies – external knowledge search, clusters, collaboration and regional value chains – help firms in Ghana and Tanzania to circumvent the many constraints they face in their day-to-day operations. In terms of policy, the chapter suggests that there is a need for policy actions that directly help to support and promote open innovation strategies within and between formal and informal sectors