BackgroundMultiple studies have reported the profound influence of various climate factors on dengue fever infection, while the effects of joint exposure to warm and wet environment, a condition favouring dengue vectors, on disease transmission were less evaluated. This study aims to investigate the impact of various compound temperature, rainfall, and relative humidity exposures on dengue fever infection in the South and Southeast Asia regions. MethodsWeekly dengue fever surveillance data from 2012 to 2020 were collected from 48 locations in four countries named Singapore (1 location), Sri Lanka (15 locations), Malaysia (9 locations), and Thailand (23 locations, with 11 locations having different study periods). The distributed lag non-linear models were built to assess the impacts of compound temperature, rainfall, and relative humidity exposures on dengue fever infection risks. ResultsA total of 1,359,993 dengue fever cases were reported with 9.33%, 24.02%, 48.73%, and 17.91% cases contributed by Singapore, Sri Lanka, Malaysia, and Thailand, respectively. Compared to non-warm-non-wet, compound warm-wet was associated with an increased dengue risk (RR:1.32, 95% CI:1.21–1.44). Compared to moderate temperature-humidity, warm-wet environment was also associated with an increase in dengue risk (RR:1.37, 95% CI:1.22–1.55). In comparison to weeks with moderate temperature-rainfall, warm-wet weeks was linked to an elevated dengue risk (RR:1.39, 95% CI:1.27–1.52), whereas cold-dry weather would significantly reduce the infection risk (RR:0.70, 95% CI:0.62–0.80). Modification effects showed that the hot effect on dengue infection was more pronounced under higher humidity, while the impact of rainfall increased with warmer temperature. ConclusionWarm-wet events were associated with an increased dengue fever risk, while the infection risk would decline in cold-dry environment, and modification effects exist among exposures. Findings from this study highlight the importance of considering joint temperature, humidity, and rainfall dependency of dengue fever infection in disease prevention and control.