Transformational change is urgently needed to address planetary health challenges in cities. Through an interdisciplinary overview of the literature, we consider how to frame and unpack city-level transformation towards synergistic benefits for urban health and environmental sustainability. By describing the characteristics of a 'healthy sustainable city' and by bringing together the ideas underlying frameworks for health and sustainability, we develop a conceptual understanding of how cities may progress towards achieving significant improvements in health and the environment. We investigate how urban change works, and build a theoretical understanding of how urban change may be directed to integrate health and sustainability. We conclude that urban transformation needs to be a multi-scalar process across city sectors to meet the scale, speed and form of change required. We propose that this can best be achieved in practice through a composition of mechanisms, including strengthening city governance, enabling technological and social innovations, applying sustainable urban planning and infrastructure development, and impelling social behaviour change; supported by systems-driven policy and practice-focused scientific evidence.