This article sets the scene for the special issue of Cities & Health Journal on ‘Transforming cities and health: policy, innovation and practice.’ It focuses on systematic transformations to meet sustainability and climate goals whilst also placing health at the heart of policy change and action. Our intention is to raise broad issues drawing on multiple disciplines and provoke engagement with this area of underachievement. We ask: ● How do we achieve action and momentum in transformational change? ● What are the key components for future transformations in terms of governance, business models, time and sequencing, scaling, leadership and imagination? ● Are there limits and barriers to what can be achieved? ● Do these demands require a more radical and fundamental change and strategic direction? In responding we note the policy-action gap and the failure to recognise the complexity in policy responses, the continuing growth of cities and the ongoing inability to address basic health needs, and we speculate about the changes that affect the context in which we work over the next decade. We highlight two case studies, where we are involved, that attempt to close the implementation gap and progress transformations. We then offer some further reflections in relation to research and practice in attempting to transform cities and health together to meet the Paris Agreement on climate change, the implementation of the UN SDGs and actions on biodiversity. In discussion, we return to the current pandemic and what this tells us about this moment, future transformations and the possibilities and limits to action.