Dengue fever is one of the most common vector-borne diseases in the world and is mainly affected by the interaction of meteorological, human and land-use factors. This study aims to identify the impact of meteorological, human and land-use factors on dengue fever cases, involving the interplay between multiple factors. The analyses identified the statistically significant determinants affecting the transmission of dengue fever, employing cross-correlation analysis and the geo-detector model. This study was conducted in Guangzhou, China, using the data of confirmed cases of dengue fever, daily meteorological records, population density distribution and land-use distribution. The findings highlighted that the dengue fever hotspots were mainly distributed in the old city center of Guangzhou and were significantly shaped by meteorological, land-use and human factors. Meteorological factors including minimum temperature, maximum temperature, atmospheric pressure and relative humidity were correlated with the transmission of dengue fever. Minimum temperature, maximum temperature and relative humidity presented a statistically significant positive correlation with dengue fever cases, while atmospheric pressure presented statistically significant negative correlation. Minimum temperature, maximum temperature, atmospheric pressure and humidity have lag effects on the transmission of dengue fever. The population, community age, subway network density, road network density and ponds presented a statistically significant positive correlation with the number of dengue fever cases, and the interaction among land-use and human factors could enhance dengue fever transmission. The ponds were the most important interaction factors, which might strengthen the influence of other factors on dengue fever transmission. Our findings have implications for pre-emptive dengue fever control.