Factors such as population growth, urban migration and climate change, are placing ever greater demands on health around the world. Cities are becoming the frontline in providing the future of healthcare, with more than half of the world’s population now living in urban environments, which is forecasted to be nearly 70% by 2050. There is therefore a growing need to identify emerging and future challenges that cities will face, identifying trends for priority issues such as ageing populations, pandemic risks and climate change. As well as indicators of current and expected future readiness for these challenges. We used design research to determine emerging and future challenges for cities to deliver healthcare. This included 8 forty minute phone interviews and 6 workshops with subject matter experts in healthcare provision from cities across three continents (North America, Europe, Africa), as well as literature reviews. The 3 speculative design workshops involved participatory design research, exploring design futures to identify emerging and likely future challenges. The qualitative data collected was synthesised with existential risks identified from literature reviews, grouping key challenges. We then, through creative engagement approaches with experts and designers in a final workshop, identified potential indicators for these key challenges. We have determined emerging and likely future challenges for health in cities, ranging from social cohesion to emerging technologies, including age friendliness, green space, and drug resistance. Grouping them into four areas: ‘ageing & lifestyle’, ‘environment & climate’, ‘innovation & technology’, and ‘other existential risks’. For ‘ageing & lifestyle’ identifying indicators for lifestyle conditions, work-life balance, managing conditions, and supporting independence. For ‘environment & climate’ identifying indicators for the built environment, climate change, green economy, and the social environment. For ‘innovation & technology’ identifying indicators for cultures of innovation, digital infrastructure, emerging technologies, and innovative practices. For ‘other existential risks’ identifying indicators for pandemics, antibiotic resistance, and anti-vaccination. By synthesising the knowledge of experts with literature reviews, we have determined the key emerging and future challenges facing cities. We have categorised these into four areas, and identified indicators for current and future readiness. Knowing these likely health challenges, we can prepare to manage them better. Furthermore, policymakers and researchers, working in public health and healthcare provision, can make use of the identified indicators. Next steps would be to collate and extract data for individual cities, for example by these cities for direct action or by a third party for comparative study.