In this study the online meteorological and chemical transport model “Weather Research and Forecasting coupled with Chemistry” (WRF/Chem) is implemented over Cyprus and evaluated against ground-based air quality and meteorological observations. Hourly O3 concentrations are strongly overestimated and a reduction in the lateral boundaries of ozone by 30% improved model agreement with observations. Utilization of grid spacing closer to the resolution of the emission data leads to an improvement in the simulation of air pollutants, while further reduction of the grid spacing mostly impacts the model performance related to meteorological parameters. The method of speciation of volatile organic compounds can also affect model results. Reduction of NOx emissions can reduce fine particulate (PM2.5) levels relatively effectively due to the important role of nitrate over Cyprus. The present case study indicates that the performance of the WRF/Chem model is reasonable for air quality and meteorological variables over Cyprus when boundary conditions are cautiously adjusted or improved, while there is a need to pursue a high-resolution local emission inventory.