Urban overheating has become an increasingly pressing issue in cities all over the world. This study explores the outdoor microclimate and thermal comfort conditions in a representative area of “El Almendral”, a historic neighborhood in Valparaíso, Chile. The research combines on-site measurements with climate simulations using ENVI-met to evaluate the impact of several intervention strategies on both climatic variables and human thermal perception. A set of nine scenarios was developed, including green and blue infrastructure strategies, as well as surface reflectivity enhancements. Simulations were configured for a 24-h period around the summer solstice using local climate data, while thermal comfort was assessed through the Universal Thermal Climate Index (UTCI). The findings highlight important divergences between air temperature reduction and thermal comfort outcomes, emphasizing the value of integrating human-centered metrics into microclimate analysis. The study reveals that strategies traditionally seen as effective from a climatic perspective may not necessarily align with improved thermal perception.