The design of our cities, their planning, and management must be increasingly oriented towards sustainability, identifying solutions that can systemically address problems on a city scale, namely urban heat islands, rainwater runoff, storms, and acoustic issues. This study begins by evaluating the impact of a green area on pedestrian comfort in the historical center of Naples, employing an experimental and numerical approach. Temperature, relative humidity, and CO2 concentration were measured at three significant points in a historical quarter in “Chiaia” district (Naples): a) in the center of the square “Piazza del Martiri” in the sun, b) in the center of the same square in the shade, and c) in the shade of the vegetation, under the effect of transpiration of deep trees. Then, these measures are used for the calibration of a numerical model developed in an environmental analysis software. The numerical approach has been used to predict the impact of possible mitigation scenarios, by increasing the vegetation and varying the density of the canopy, using non-white cool materials for the urban surfaces and for the facades and roofs of the surrounding historical buildings, and adding fountains. These strategies have a positive effect on urban temperatures and outdoor comfort, in densely urbanized contexts. The findings are finally used to identify the best design solutions, to improve pedestrian comfort and reduce the urban heat, without affecting the historical value of the urban district.