Dengue fever has continuously been a disease burden in Vietnam during the last 20 years, particularly in the Mekong Delta region (MDR), which is one of the most vulnerable to climate change. Variations in temperature and precipitation are likely to alter the incidence and distribution of vector-borne diseases such as dengue. This study focuses on assessing dengue risk via the vulnerability concept, which is composed of exposure and susceptibility using a combined approach of mapping and modelling for the MDR of Vietnam during the period between 2001 and 2016. Multisource remote sensing data from Global Satellite Mapping of Precipitation (GSMaP) and Moderate Resolution Imaging Spectrophotometer (MODIS) was used for presenting climate and environment variables in mapping and modelling vulnerability. Monthly and yearly maps of vulnerability to dengue in the MDR, produced for 15-year period, aided analysis of the temporal and spatial patterns of vulnerability to dengue in the study region and were used for constructing time-series modelling of vulnerability for the following year. The results showed that there is a clear seasonal variation in the vulnerability due to variability of the climate factor and its strong dispersion across the study region, with higher vulnerability in the scattered areas of urban and mixed horticulture land and lower vulnerability in areas covered by forest and bare soil lands. The Pearson’s correlation was applied to evaluate the association between dengue rates and vulnerability values aggregated at the provincial level. Reasonable linear association, with correlation coefficients of 0.41–0.63, was found in two-thirds of the provinces. The predicted vulnerabilities to dengue during 2016 were comparable with the estimated values and trends for most provinces of the MDR. Our demonstrated approach with integrated geospatial data seems to be a promising tool in supporting the public health sector in assessing potential space and time of a subsequent increase in vulnerability to dengue, particularly in the context of climate change.