The world is now predominantly urban; rapid and uncontrolled urbanisation continues across low-income and middle-income countries (LMICs). Health systems are struggling to respond to the challenges that urbanisation brings. While better-off urbanites can reap the benefits from the ‘urban advantage’, the poorest, particularly slum dwellers and the homeless, frequently experience worse health outcomes than their rural counterparts. In this position paper, we analyse the challenges urbanisation presents to health systems by drawing on examples from four LMICs: Nigeria, Ghana, Nepal and Bangladesh. Key challenges include: responding to the rising tide of non-communicable diseases and to the wider determinants of health, strengthening urban health governance to enable multisectoral responses, provision of accessible, quality primary healthcare and prevention from a plurality of providers. We consider how these challenges necessitate a rethink of our conceptualisation of health systems. We propose an urban health systems model that focuses on: multisectoral approaches that look beyond the health sector to act on the determinants of health; accountability to, and engagement with, urban residents through participatory decision making; and responses that recognise the plurality of health service providers. Within this model, we explicitly recognise the role of data and evidence to act as glue holding together this complex system and allowing incremental progress in equitable improvement in the health of urban populations.