The climate affects how a city’s outdoor spaces are utilized. It is more likely that people will use and appreciate public areas designed for pedestrian use, such as parks, squares, streets, and foot-cycle pathways, when they provide a comfortable and healthy environment. A predicted increase in global temperature has made the climate uncomfortable, especially during the summer when heat stress is strengthened and anticipated. This phenomenon is more severe in urban areas, often affected by the Urban Heat Island (UHI) effect. Since the spatial characteristics of a city influence its climate, urban design can be deployed to mitigate the combined effects of climate change and UHI. This research is conducted to study the UHI effect on thermal comfort in an urban open space in Rome (Italy) and aims at identifying and implementing a methodology that urban designers can follow to reduce the impact of urban heat islands and increase thermal comfort in urban outdoor space. This study is based on an urban design concept adopting the Sustainable Development Goals as guidelines; it investigates how UHI’s effect affects the use of public space and examines the influence of urban microclimatic conditions on the thermal perception of users through PET, PMV and PPD values, that were assessed through simulations with ENVI-MET software. The study thus proposes a redesign for the site in Rome, with a masterplan based on sustainable design principles, aimed at improving the microclimatic conditions in the site. The design solution was then validated through ex post simulations.