Recent intensification of urban heat islands (UHIs) poses a great threat to public health, promoting studies on UHI mitigation strategies. However, the question about the transferability of a mitigation method from a specific city to another remains largely unanswered. This study compares common UHI mitigation strategies (including green roofs, cool roofs, and changing urban building structure) for two Chinese megacities suffered from summer heat stress: Xi’an with a semi-humid climate and Wuhan with a humid climate, through the use of the urbanized-high-resolution land data assimilation system (u-HRLDAS) modeling tool and remote-sensing data. The results reveal that (1) all UHI mitigation strategies work more efficiently for Xi’an than that for Wuhan, particularly for the strategy of modifying urban fraction and associated green roof fraction; (2) the difference in cooling efficacy between the two cities is insignificant during relatively cool periods. Under hot weather conditions, the best choice of UHI mitigation strategy depends on urban land use categories in Xi’an; and (3) the differences in UHI mitigation efficacy are likely caused by the differing regional climate. This study highlights the need to better understand the transferability of UHI mitigation strategies in different climate zones.