Traffic emissions, overpopulation, and poor urban planning have degraded the environmental quality of the Greater Cairo megacity. As road dust is considered the main sink of pollutants in urban environments, thirty road dust samples from six major roads were collected. ICP-OES was used to analyze the samples in order to determine the contamination grade using the pollution indices, decipher metal sources and geochemical associations using multivariate analysis, and evaluate the ecological and human health risks. The average contents of heavy metals were arranged in decreasing order: Fe (1181.12), Zn (201.36), Pb (66.10), Ni (32.42), Cu (26.07), Cr (26.00), Co (14.78), As (2.76), and Hg (0.93) mg/kg. The spatial pattern showed that new urban communities exhibited lower contamination levels compared to unplanned old districts, especially for traffic elements (Pb, Zn, and Cu). The highest Igeo mean value was observed for Hg (3.34) followed by Zn (1.34), Pb (1.24), Ni (0.10), As (− 0.19), Co (− 0.24), Cu (− 0.73), and Cr (− 1.05). Additionally, CF values indicated very high contamination levels for Pb and Zn, whereas the highest PLI value was observed at Ramses Street. All EF values were higher than 1.5, indicating the anthropogenic enrichment of metals. RI values classified Cairo as a region with considerable ecological risk, observing that Hg was the main contributor. Correlation analysis and PCA showed that Pb and Zn originated from vehicle exhaust, Hg, Cu, and As from domestic and industrial activities, and Fe and Co from natural origin. Cr and Ni exhibited potential carcinogenic risks for children through ingestion; conversely, the non-carcinogenic risks were within safe levels. As a result, the use of clean energy is recommended to mitigate the accumulation of heavy metals in road dust and to improve the quality of life.
