Climate change and extreme weather are increasing global disease burdens, but the association between weather conditions and hospital admissions in Macau remains unclear. This study was performed in the context of Macau, China. It analyzed daily hospital admissions from Macau’s hospitals with emergency departments and local meteorological data (2017–2022) using distributed lag nonlinear models with 21-day lag effects. Results revealed that 14.5 °C was associated with the lowest risk of hospital admissions. Colder temperatures exhibited prolonged effects, elevating risks for up to 21 days, while hotter temperatures’ impacts were shorter. Compared with mean relative humidity (81%), the risk was lowest when relative humidity was 33% (RR = 0.87, 95% CI: 0.66–1.14), and the risk was highest when relative humidity was 100% (RR = 1.50, 95% CI: 1.15–1.94). The effects of these weather conditions on hospital admissions varied by disease and age, with smaller differences between sexes. The increased hospital admissions in Macau are associated with hotter and colder temperatures, as well as humidity. As climate change intensifies weather extremes, healthcare systems may face escalating demands, necessitating targeted prevention strategies for high-risk groups and optimized resource allocation.