Air pollution in opencast coal mine areas is a critical issue, resulting in harmful severe effects on human health. Therefore, it is essential to understand the air pollution factors and to assess the risks to humans. This study evaluated the potential risks (carcinogen and non-carcinogen) of inhalation exposure to PM10-bound heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) in an open pit mine in northern Colombia. During February-May 2022, PM10 samples were collected at eight sites. Heavy metals (i.e., Al, Cr(VI), Mn, Cu, Zn, As, Pb) and PAHs (thirteen priority PAHs, and one non-priority PAH) levels linked to PM10 were analyzed by X-ray fluorescence and gas chromatography–mass spectrometry, respectively. PM10 concentrations were found to range between 4.70 and 59.90 µg m−3. Out of the three different zones of the study area (i.e., North Zone, South Zone, and Populated Zone), the North Zone recorded the highest daily average concentrations of Cr(VI) (104.16 ng m−3), Mn (28.39 ng m−3), Cu (33.75 ng m−3), Zn (57.99 ng m−3), As (44.92 ng m−3), and Pb (27.13 ng m−3). The fraction of the analyzed heavy metals at all monitoring sites was 82%–89% for Al, followed by Cr(VI) with 3%–6%. Cr(VI) was the major contributor to the carcinogenic risk values, while Cu, Cr(VI), and As were the main drivers for the non-carcinogenic risk. The average cancer risk range for heavy metals was 3.30 × 10–04 –5.47 × 10–04. On the other hand, the cancer risk for PAHs exposure was acceptable. The average incremental lifetime cancer risk (ILCR) values varied between 2.87 × 10–07 and 4.21 × 10–07. Benzo[a]pyrene contributed to 54%–56% of the total risk from inhalation of PM10-bound PAHs, while Indeno[1,2,3-cd]pyrene contributed to 16%–19%. Based on the Monte Carlo sensitivity analysis, exposure to Cr(VI) was the main factor affecting cancer risk in the North, South, and Populated Zones. A suitable risk assessment and management plan requires understanding PM10-bound heavy metals and PAHs concentration levels as well as their potential health risks, mainly in open-cast coal mine zones. Our study found that people living near open-pit mines face potential health risks, so it is crucial to establish policies and regulations to control emission sources.