The chapter reflects on research that rethinks classic concerns of comparative and international education – the relationships between education and work and the role of education in development. The promises of knowledge-led economic growth have instead yielded increased inequality, poverty, environmental degradation and a decline in the quality of life for the majority, whether in advanced economies of the North, or least developed economies of the South. For education and training systems, the ability to understand these complex social, economic and technological challenges, interpret implications and integrate new practices in response, becomes critical. We reflect on the use of an innovation systems approach in the South, over time, to investigate the ways in which higher education responds to and interacts with, demand for skills from the economy. By highlighting the role of university actors and their interaction in networks, comparative and international researchers can move beyond dominant human capital accounts that focus only on the responsibility of higher education to become more responsive to firms, or on individuals to prepare themselves to be more employable, in a mechanistic reactive manner. This is a promising new emphasis for comparative research.