As urban overheating is increasing, there is a strong public interest towards mitigation strategies to enhance comfortable urban spaces, for their role in supporting urban metabolism and social life. The study presents an assessment of the existing thermal comfort and usage of San Silvestro Square in Rome during the summer, and performs the simulation of cooling strategies scenarios, to understand their mitigation potential for renovation projects. The first stage concerns a field analysis of the thermal and radiative environment on the 1st and 2nd of August 2014, including meteorological measurements and unobtrusive observations, to understand how people experience and respond to extreme microclimate conditions. In the second stage, the research proposes scenario simulations on the same day to examine the influence of cool colored materials, trees and vegetative surfaces on thermal comfort. The thermal comfort assessment was based on Physiologically Equivalent Temperature (PET), whereas microclimatic simulations were conducted with CFD calculations (ENVImet v.4.3.1). The first stage shows a strong relationship between lower PET values and attendance rate, depending on daily shading patterns. The second stage shows a relevant improvement of thermal comfort, with PET values of −12 °C comparing to the no-intervention scenario, associated with a combination of cool materials and trees.