Extreme events in the Mediterranean have increased in frequency and intensity during the last decade, and this trend is expected to continue in the future. Characterising the features of extremes using observations and well-established datasets is critical for understanding the processes and development of extreme weather, as well as improving forecast. This study uses observational data collected during the Mediterranean Experiment for Sea Salt And Dust Ice Nuclei (MESSA-DIN) from July to September 2021 to characterise the synoptic analysis of the severe summer of 2021. The analysis focuses primarily on water vapour fluxes, humidity, convective parameters, and the role of aerosols in cloud formation. Furthermore, we compare the findings to the widely known atmospheric reanalysis ERA5, pointing out agreements and inconsistencies with observations, as well as discussing aspects that can improve modelling activities for addressing and forecasting extreme weather, with a focus on the extreme flooding that affected Central Europe in July 2021. The findings show the crucial role of water vapour fluxes in regional climate events, emphasizing the need for high- resolution data from microwave radiometers and atmospheric profilers to verify and improve predictions under complex atmospheric conditions. ERA5 performed rather well in synoptic representation, but it exhibited a dry bias in RH values, which affected the accurate representation of water vapour fluxes. By comparing the ERA5 RH bias with upper-air measurements available during the campaign period at the Potenza GRUAN (GCOS Reference Upper-Air Network) site, in South Italy, the bias was further examined, showing to exhibit an irregular behavior at different sites. The findings also emphasize the need for improving reanalysis model performance in complex terrain conditions, particularly near coastal areas, as well as the use of km-scale models for mesoscale research and dealing with extreme weather.