Urban areas are uniquely vulnerable to heat waves (HWs), due to high human exposure and the exacerbating influence of urban heat islands (UHIs). Notably, when urban temperature rises surpass those in neighboring rural areas during HWs, this can trigger “synergistic interactions” between HWs and UHIs, thereby heightening urban heat-related risks. It is therefore crucial to examine the UHIs response to HWs in different climate regimes for enhancing urban resilience strategies against heat-related disasters. In this study, we investigate the interactions between HWs and UHIs at a spatial resolution of 1/8° over the Contiguous United States (CONUS), utilizing an urbanized earth system model CESM2. Our findings demonstrate that during the historical period of 1981-2020, the daily mean UHI intensity increases under HWs over the eastern and western US but declines in mid-west region. We identify the sensitivity of urban and rural evapotranspiration to varying environmental stresses as a pivotal factor in understanding how HWs affect the daily mean UHI intensity. Furthermore, we investigate the projected evolution of the intricate interplay between HWs and UHIs in in future warmer climates (2060-2099), while concurrently exploring the fundamental physical mechanisms involved. The findings of this study highlight the importance of properly parameterizing the sensitivity of urban and rural evapotranspiration to various environmental stresses in climate and earth system models.