Along with global climate change and the worldwide heat island phenomenon, developing climatic methods and planning practices for the benefit of thermal comfort is of increasing interest. Studies have focused on urban streets, studying the aspect ratio, the orientation, street vegetation patterns, etc. and how they affect thermal comfort. While the role of vegetation is undeniable, this paper asks the question whether the effects of a tree configuration does not vary under different street configurations, and if yes, how to select tree species and determine their appropriate layout. Here, an analytical framework is proposed to test the different tree configurations (changing one variable at a time) with the least favorable street configuration. It is confirmed that the east–west oriented streets are the least favorable cases and denser tree canopies are better for cooling. The interval between the trees are observed to have an optimal effect when it is equal to the crown width at maturity. Furthermore, the results show that the heat mitigation rate of a tree configuration is not linearly improved by the Aspect Ratio (AR). In the case of Shantou city, the improvement of thermal comfort slows down when the AR reaches 1.5 while Mangifera indica planted with 10 m intervals is recommended among the common street-tree species. Other species could be used also, but should meet the requirements of the canopy density and the interval of layout. The paper does not consider other configuration options such as asymmetrical cases of street geometry and one-side or axial tree planting, etc., but the framework allows for adding such options and simulating thermal comfort for a greater number of scenarios.