Droughts and heatwaves in the Mediterranean can induce plant activity decline and severe wildfires leading to considerable economic, social and environmental damages. This study aims at statistically quantifying the isolated and combined impacts of these extreme events based on a combination of regional land surface-atmosphere modeling and satellite observations of surface properties (MODIS). A simulation by the RegIPSL coupled regional model (ORCHIDEE-WRF) over the 1979-2016 period in the Western Mediterranean is used to identify heatwaves and droughts. After an evaluation of the model performance against surface observations of temperature and precipitation, a spatio-temporal analysis is conducted using specific indicators of extreme events: Percentile Limit Anomalies (PLA) and the Standardized Precipitation Evapotranspiration Index (SPEI). The impact on vegetation and wildfires is assessed using the MODIS observations of Leaf Area Index (LAI), burned area (BA) and fire radiative power (FRP), clustered by simulated extreme weather events. Due to water stress, droughts lead to significant biomass decrease (− 10% LAI on average and reaching − 23% in some areas). The isolated effect of heatwaves is smaller (∼ − 3% LAI) so that the combined effect is dominated by the impact of droughts. Heatwaves and droughts significantly exacerbate wildfire regimes. Through synergistic effects, simultaneous droughts and heatwaves increase BA and FRP by 2.1 and 2.9 times, respectively, compared to normal conditions. By reducing biomass, droughts slightly decrease fuel availability. However, our results show that the inter-annual variation in fire activity is mainly driven by weather conditions rather than fuel load.