Introduction: Motor transport with internal combustion engines powered by diesel fuel and gasoline is one of the main sources of ambient air pollution since its emissions pose an urgent medical and environmental challenge. The objective of the study was to identify priority pollutants from emissions of motor vehicles powered by internal combustion engines based on the results of a systematic review in order to substantiate the main preventive strategy to mitigate the associated public health adverse effects. Methods: We did keyword search for relevant publications in several electronic databases, such as the Russian Science Citation Index, CyberLeninka, Scopus, and WoS. Research papers published in 2000–2021 were selected for the analysis. Out of 103 topical full-text publications, 59 works met the criteria for inclusion in the systematic review. Results: We observed that atmospheric emissions of internal combustion engines represent a complex agglomeration of gases, vapors, and particulate matter. The chemicals present in the emissions impair the oxygen transport function by inhibiting cellular respiration, cause irritation of mucous membranes, have mutagenic and carcinogenic effects, contribute to the occurrence of acid rains and to global warming. The biological effect of airborne particles largely depends on their size. It has been established that an increase in the number of airborne particles with an aerodynamic diameter less than 10 μm is associated with the risk of endothelial inflammation, thrombosis, increased cell permeability, and DNA methylation. It has been also demonstrated that a 5 µg/m3 increment in ambient concentrations of fine particles (< 2.5 μm) causes a 7 % increase in the mortality rate. At the same time, PM2.5 exposure-related risks of excess deaths from cardiovascular diseases are twice as high as those posed by exposure to PM10. Conclusions: Diesel and gasoline engine exhausts are a significant risk factor for human health. An effective preventive strategy should be aimed at replacing heavy hydrocarbon motor fuels by compressed gas using hydrogen cells and electric motors.