With global warming and rapid urbanization, the microclimate in the Lingnan region is prone to health problems, such as pyrexia and infectious diseases, and the average annual number of heatwave-related deaths is rising rapidly. The large-scale regeneration of traditional neighborhoods in Lingnan under high-quality development is underway, which has implications for the thermal comfort of microclimatic environments. This study focused on the impact of different building unit types and spatial patterns on thermal comfort in the Donghuali traditional neighborhood of Foshan City as an example. We extracted eight basic morphological units and designed a prototype block of 400 m × 400 m. In the Rhinoceros & Grasshopper parametric software 6.7, a variety of plug-ins were integrated to establish a platform with parametric modeling, microclimate simulation and evaluation, and optimal design for thermal comfort. Through experiments, the effects of new single-type and new composite building units on thermal comfort were investigated, and the correlation equations between spatial morphology and microclimate comfort in Lingnan traditional neighborhoods were established. Finally, the multi-objective genetic optimization of thermal comfort was carried out as an example of real block renewal, which provides a practical reference for the planning and design of traditional blocks.