This chapter discusses continuities and breaks between Freeman’s List-Schumpeter synthesis and more recent ideas on directionality of innovation in interdisciplinary research and the policy framework of mission-oriented innovation. These ideas are based on an aim of moving beyond the systems approach, and towards a new kind of innovation policy which is to be directional and transformative in nature. On the one hand, previous innovation systems approaches are being criticized for lacking an attentiveness towards matters of directionality. On the other hand, the theoretical underpinnings of current mission-oriented innovation policies involve revaluations of the merits of Schumpeter’s own writings on entrepreneurship and finance. This chapter argues that more recent discourse on the directionality of innovation and transformative change represents less of a break with Freeman’s List-Schumpeter synthesis and the systems of innovation approach, than it is a continuation of its commitment to directional political economy in a cyclically evolving late capitalist society.