Lack of attention to thermal comfort in urban squares, particularly under harsh climatic conditions, can lead to reduced urban livability and weaken the conditions that support citizens’ presence and activities. Naqsh-e Jahan Square and Imam Ali Square, as two prominent urban squares that play a significant role in the urban life of Isfahan, have experienced unfavorable thermal comfort conditions due to physical-historical transformations (from the Safavid period to present) as well as structural interventions. The aim of this study is to evaluate and comparatively assess the thermal comfort conditions of these squares using microclimate simulation techniques. Accordingly, the main research question is: How can the thermal comfort quality of Naqsh-e Jahan Square and Imam Ali Square be evaluated in comparison? To achieve this objective, the research adopts an evaluative approach through a multiple case study strategy, incorporating meteorological data analysis, three-dimensional modeling using ENVI-met 5.6, and assessment of existing conditions based on PMV thermal comfort index. According to the findings, both squares experience reduced thermal comfort and urban heat island phenomenon. However, Naqsh-e Jahan Square exhibits conditions closer to human thermal comfort compared to Imam Ali Square, providing a more favorable microclimate for a wide range of activities and the presence of citizens. The results indicate that certain spatial–physical factors, such as the covered bazaar, enclosing walls, climate-adapted materials, natural elements including surface water network and vegetation, as well as complementary structures such as semi-open wooden pavilions and temporary canopies, contribute to thermal comfort throughout all seasons, particularly during peak thermal stress days, and enhance the quality of life.