The aim of this paper is to evaluate the surface concentration of nitrogen dioxide (NO2) inferred from the Sentinel-5 Precursor Tropospheric Monitoring Instrument (S5P/TROPOMI) NO2 tropospheric column densities over Central Europe for two time periods, summer 2019 and winter 2019–2020. Simulations of the NO2 tropospheric vertical column densities and surface concentrations from the Long-Term Ozone Simulation–European Operational Smog (LOTOS-EUROS) chemical transport model are also applied in the methodology. More than two hundred in situ air quality monitoring stations, reporting to the European Environment Agency (EEA) air quality database, are used to carry out comparisons with the model simulations and the spaceborne inferred surface concentrations. Stations are separated into seven types (urban traffic, suburban traffic, urban background, suburban background, rural background, suburban industrial and rural industrial) in order to examine the strengths and shortcomings of the different air quality markers, namely the NO2 vertical column densities and NO2 surface concentrations. S5P/TROPOMI NO2 surface concentrations are inferred by multiplying the fraction of the satellite and model NO2 vertical column densities with the model surface concentrations. The estimated inferred TROPOMI NO2 surface concentrations are examined further with the altering of three influencing factors: the model vertical leveling scheme, the versions of the TROPOMI NO2 data and the air mass factors applied to the satellite and model NO2 vertical column densities. Overall, the inferred TROPOMI NO2 surface concentrations show a better correlation with the in situ measurements for both time periods and all station types, especially for the industrial stations (R > 0.6) in winter. The calculated correlation for background stations is moderate for both periods (R~0.5 in summer and R > 0.5 in winter), whereas for traffic stations it improves in the winter (from 0.20 to 0.50). After the implementation of the air mass factors from the local model, the bias is significantly reduced for most of the station types, especially in winter for the background stations, ranging from +0.49% for the urban background to +10.37% for the rural background stations. The mean relative bias in winter between the inferred S5P/TROPOMI NO2 surface concentrations and the ground-based measurements for industrial stations is about −15%, whereas for traffic urban stations it is approximately −25%. In summer, biases are generally higher for all station types, especially for the traffic stations (~−75%), ranging from −54% to −30% for the background and industrial stations.