Atmospheric nitrogen dioxide (NO2) pollution is a major health and social challenge in South African induced mainly by fossil fuel combustions for power generation, transportation and domestic biomass burning for indoor activities. The pollution level is moderated by various environmental and social factors, yet previous studies made use of limited factors or focussed on only industrialised regions ignoring the contributions in large parts of the country. There is a need to assess how socio-environmenral factors, which inherently exhibit variations across space, influence the pollution levels in South Africa. This study therefore aimed to predict annual tropospheric NO2 column density using socio-environmental variables that are widely proven in the literature as sources and sinks of pollution. The environmental variables used to predict NO2 included remotely sensed Enhanced Vegetation Index (EVI), Land Surface Temperature and Aerosol Optical Depth (AOD) while the social data, which were obtained from national household surveys, included energy sources data, settlement patterns, gender and age statistics aggregated at municipality scale. The prediction was accomplished by applying the Multiscale Geographically Weighted Regression that fine-tunes the spatial scale of each variable when building geographically localised relationships. The model returned an overall R2 of 0.92, indicating good predicting performance and the significance of the socio-environmental variables in estimating NO2 in South Africa. From the environmental variables, AOD had the most influence in increasing NO2 pollution while vegetation represented by EVI had the opposite effect of reducing the pollution level. Among the social variables, household electricity and wood usage had the most significant contributions to pollution. Communal residential arrangements significantly reduced NO2, while informal settlements showed the opposite effect. The female proportion was the most important demographic variable in reducing NO2. Age groups had mixed effects on NO2 pollution, with the mid-age group (20-29) being the most important contributor to NO2 emission. The findings of the current study provide evidence that NO2 pollution is explained by socio-economic variables that vary widely across space. This can be achieved reliably using the MGWR approach that produces strong models suited to each locality.