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Mining is responsible for the release of metallic pollutants and radioactive materials into the environment, which have the potential to disrupt ecosystems and pose significant risks to human health. Significant mining activity is concentrated in the municipality of Caetité (northeastern Brazil), where Latin America's only active uranium mine and significant iron ore deposits are located. Although previous studies have shown that the regional soil and water resources are highly contaminated by various toxic elements and that exposure to these elements is known to have adverse effects on human health, the health risks in this mining region have never been assessed. The aim of this unprecedented comprehensive investigation was to assess the health, radiological and ecological risks in this mining region, which is home to nearly 100,000 people. To achieve our goal, soil and water samples were collected in the vicinity of the mines and in the main settlements in the region. Fifteen metallic toxic elements were determined using Instrumental Neutron Activation Analysis and Inductively Coupled Plasma Optical Emission Spectrometry. The HERisk code, which follows the main methodological guidelines for risk assessment, was used to quantify human health, radiological and ecological indices. The average values of the total risk and cancer risk indices indicated that region falls into the moderate risk category (1.0 ≤ HI tot  < 4.0). However, 63% of the sites had high risk values, with Fe, Co and As being the metals contributing most to total and cancer risk, respectively. Near the mining areas, the potential ecological risk can be considered extreme (PERI ≥ 600). The values of the calculated radiological indices correspond to typical values ​​in natural uranium areas. However, in the communities near the mine, the dose values are slightly above the permissible limit (1 mSv y -1 ), so they must be continuously monitored, and risk mitigation measures must be taken., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)