Climate and weather conditions have a profound influence on human comfort and discomfort sense. In addition, the impact of emissions and human activities on air quality seems to be scientifically indisputable. The maintenance of low levels of environmental nuisance in areas of high environmental and cultural interest, such as some Greek islands, is becoming increasingly important. Thus, exploring the combination of the effect of air quality and climate comfort in a high-traffic area falls within the scope of the principles and practices of sustainable development of such areas. The current study aims to shed some light on this field for the case of Rhodes city, located in eastern Mediterranean, during the summer of 2021. For the analysis, measurements of the concentration of pollutants (PM_2.5, NO_X and O₃) and meteorological recordings (wind speed, wind direction and temperature) from a mobile air quality system located in the center of Rhodes city were conducted. Furthermore, meteorological data from the ERA5 reanalysis (wind speed, temperature, relative humidity, precipitation, cloud cover and height of boundary layer) over a geographical domain around Rhodes Island are also included in the study. Results show that climate conditions and emissions are closely linked to traffic and tourism activities, which in turn affect the variability of pollutant concentrations. The calculation of the discomfort index shows that during the period of higher levels of air pollution, more than half of the population of Rhodes city feels discomfort while, the holiday climate index values show that the climatic conditions are suitable for tourist activities. In conclusion, this study could enhance our understanding of climate comfort and air quality by providing some evidence of the benefits of implementing a sustainable development policy in such tourist areas.