Background China’s Guangdong Province experienced a major dengue outbreak in 2014. Here we investigate if the weather conditions contributing to the outbreak can be elucidated by multi-scale models. Methods A multi-scale modelling framework, parameterized by available weather, vector and human case data, was used to examine the integrative effect of temperature and precipitation variation on the effective reproduction number (ERN) of dengue fever. Results With temperature in the range of 25–30 °C, increasing precipitation leads to an increase in the ERN with an average lag of 10 days. With monthly precipitation fixed, the more regular the pattern of rainfall (i.e. higher numbers of rainy days), the larger is the total number of adult mosquitoes. A rainfall distribution peaking in June and July produces a large ERN, beneficial to transmission. Climate conditions conducive to major outbreaks within a season are a combination of relatively high temperature, high precipitation peaking in June and July, and uninterrupted drizzle or regular rainfall. Conclusions Evaluating a set of weather conditions favourable to a future major dengue outbreak requires near-future prediction of temperature variation, total rainfall and its peaking times. Such information permits seasonal rapid response management decisions due to the lags between the precipitation events and the realisation of the ERN.