This article presents the results of an international research project carried out in Italy and Canada, conducted by architects, landscape architects, sociologists and medical doctors. The study originated in the conviction that health and well-being are crucial objectives integrated within the notion of a sustainable city. For this reason, the configuration of urban space plays a decisive role in defining lifestyles and can contribute to improving the welfare of citizens. Many of today’s diseases are caused by a sedentary lifestyle; it is essential, therefore, to centre prevention on the promotion of physical well-being encouraging an active lifestyle, which can be achieved by changing the urban structure. With the aim of bringing about sustainable and healthy lifestyles, streets are in vogue. Streets are meeting and experimental places, theatres of everyday life and settings for cultural events. They provide crucial urban space for people and, in the context of urban studies, offer intellectual research nourishment to reflect on this fundamental element of the structure of the city. The research project presented here is aimed at encouraging active lifestyles, walkability and the use of public transport by facilitating accessibility to four sites in Rome and Montreal, and by exploring the potential leveraging of existing infrastructures and services. The research-based design proposals start with the idea of redeveloping the system of public spaces, beginning with the increase of bicycle and pedestrian routes in relation to schools, commerce, sports facilities and archaeological heritage. The goal is to build feasible, safe, recognisable and attractive routes and well-equipped public spaces in order to discourage the use of private vehicles, especially for short trips. The projects presented here are based on a systemic vision and make use of existing, but often abandoned or undervalued, spaces and resources.