Cities are key for sustainability and the radical systemic changes required to enable equitable human development within planetary boundaries. Their particular role in this regard has become the subject of an emerging and highly interdisciplinary scientific debate. Drawing on a qualitative literature review, this paper identifies and scrutinizes the principal fields involved, asking for their respective normative orientation, interdisciplinary constitution, theories and methods used, and empirical basis to provide orientations for future research. It recognizes four salient research epistemologies, each focusing on a distinct combination of drivers of change: (A) transforming urban metabolisms and political ecologies; (B) configuring urban innovation systems for green economies; (C) building adaptive urban communities and ecosystems; and (D) empowering urban grassroots niches and social innovation. The findings suggest that future research directed at cities and systemic change towards sustainability should (1) explore interrelations between the above epistemologies, using relational geography and governance theory as boundary areas; (2) conceive of cities as places shaped by and shaping interactions between multiple socio-technical and social-ecological systems; (3) focus on agency across systems and drivers of change, and develop corresponding approaches for intervention and experimentation; and (4) rebalance the empirical basis and methods employed, strengthening transdisciplinarity in particular.