As the research on technology transfer and innovation continues to develop, there is still a need to determine which mechanisms can be used to develop entrepreneurial capabilities to enhance technology transfer. This study aims to show how mechanisms such as innovation spaces can be used to support entrepreneurs by enhancing their ability to seize opportunities of high value. This can be attributed to the development of new-generation technologies stemming from the Fourth Industrial Revolution (4IR). Thus, the objective of this study is to demonstrate innovation spaces’ role within knowledge-rich research environments such as universities, and how they enhance entrepreneurial abilities to create ventures of high value. To enhance the understanding of this concept, the important role of technologies, especially those attributable to 4IR to create entrepreneurial ventures of high value were reviewed. This was done through the lens of entrepreneurs who originate from academic environments within the context of South African universities. In order to achieve this, a theoretical overview of innovation, entrepreneurship, technology transfer and 4IR was developed. This study followed a case study methodology which allowed for an analysis of bounded entities, which—in this research—involved universities in South Africa and the innovation spaces they utilise to support entrepreneurs. The results indicated various themes and common practices across entities in South Africa, which create an ecosystem that aims to enhance technology transfer within the region by leveraging innovation spaces. This means that innovation spaces offer an early access point to technological innovation, which can emanate from academic research to accelerate the development of entrepreneurial ventures through an array of support resources and services. As such the findings show that technology transfer continues to play a pivotal role in this emerging technological paradigm, where strategies to address disruptions of 4IR require coordinated activities. It is recommended that further research be conducted based on an institutional theory approach to expand the focus of entrepreneurship, where innovation spaces are used as a launchpad in an attempt to improve their success rate.