Dust pollution is a major threat to human health and ecosystems, highly affecting both the outdoor and indoor air quality, while dust particles are an important carrier of potential toxic elements (PTEs) in urban environments. In this study, the concentrations of selected elements in indoor and outdoor dust samples, pollution and ecological risks, along with human health risk are analyzed in the highly dust-polluted cities of Ahvaz and Zabol, Iran during the spring and summer of 2017. The concentrations of elements related to industrial and urban emissions (e.g., Zn, Pb, Cu, Cr) were significantly higher in Ahvaz than Zabol. In general, weak correlations were found between the same heavy metals of indoor and outdoor dust, except for As, suggesting considerable variations in emission sources. The pollution indices revealed moderate contamination from heavy metals like Cd, As, and to some extent Zn and Pb, in the indoor dust samples, and lower contamination in outdoor dust. In both cities, ingestion was the main pathway of health risk exposure to PTEs, followed by dermal contact and inhalation, for both children and adults. The highest non-carcinogenic and cancer risks of indoor and outdoor dust were related to Cr and As, for both children and adults, while Cd and Pb through the respiratory pathway exhibited the lowest non-carcinogenic and cancer risks, respectively. The hazard index (HI) and the total cancer risk (TCR) were found in safe and tolerable levels (HI < 1 and 10−4 < TCR <10−6) in both cities, although higher in Ahvaz, while the health risk was found similar for outdoor and indoor dust in most cases.