Fundamental principles of modern cities and urban planning are challenged during the COVID-19 pandemic, such as the advantages of large city size, high density, mass transport, free use of public space, unrestricted individual mobility in cities. These principles shaped the development of cities and metropolitan areas for more than a century, but currently, there are signs that they have turned from advantage to liability. Cities Public authorities and private organisations responded to the COVID-19 crisis with a variety of policies and business practices. These countermeasures codify a valuable experience and can offer lessons about how cities can tackle another grand challenge, this of climate change. Do the measures taken during the COVID-19 crisis represent a temporal adjustment to the current health crisis? Or do they open new ways towards a new type of urban development more effective in times of environmental and health crises? We address these questions through literature review and three case studies that review policies and practices for the transformation of city ecosystems mostly affected by the COVID-19 pandemic: (a) the central business district, (b) the transport ecosystem, and (c) the tourism-hospitality ecosystem. We assess whether the measures implemented in these ecosystems shape new policy and planning models for higher readiness of cities towards grand challenges. And how, based on this experience, cities should be organized to tackle the grand challenge of environmental sustainability and climate change.