(1) Background: Although the health effects of future climate change have been examined in previous studies, few have considered additive impacts of population expansion, ageing, and adaptation. We aimed to quantify the future heat-related years of life lost (YLLs) under different Representative Concentration Pathways (RCP) scenarios and global-scale General Circulation Models (GCMs), and further to examine relative contributions of population expansion, ageing, and adaptation on these projections. (2) Methods: We used downscaled and bias-corrected projections of daily temperature from 27 GCMs under RCP2.6, 4.5, and 8.5 scenarios to quantify the potential annual heat-related YLLs in Guangzhou, China in the 2030s, 2060s, and 2090s, compared to those in the 1980s as a baseline. We also explored the modification effects of a range of population expansion, ageing, and adaptation scenarios on the heat-related YLLs. (3) Results: Global warming, particularly under the RCP8.5 scenario, would lead to a substantial increase in the heat-related YLLs in the 2030s, 2060s, and 2090s for the majority of the GCMs. For the total population, the annual heat-related YLLs under the RCP8.5 in the 2030s, 2060s, and 2090s were 2.2, 7.0, and 11.4 thousand, respectively. The heat effects would be significantly exacerbated by rapid population expansion and ageing. However, substantial heat-related YLLs could be counteracted by the increased adaptation (75% for the total population and 20% for the elderly). (4) Conclusions: The rapid population expansion and ageing coinciding with climate change may present an important health challenge in China, which, however, could be partially counteracted by the increased adaptation of individuals.