This work aims at illustrating the benefit of combining lead (Pb) biomonitoring data with toxicokinetic simulations in order to confidently identify the risk management intervention that favors the greatest reduction of blood Pb level (BLL) in children exposed to smelter emissions in a mining city from northern Quebec, Canada. The U.S. EPA’s Integrated Exposure and Uptake BioKinetic (IEUBK) model was parametrized with relevant environmental concentrations data to simulate background BLL (in average Canadian children) and local BLL (in children from the concerned community). The resulting simulations were compared with corresponding BLL biomonitoring data. Next, soil and air concentrations were lowered sequentially within the IEUBK model to values specified in Quebec’s environmental regulations. IEUBK simulations predicted mean BLL values that were similar to the measured biomonitoring values, for both the background (predicted: 0.56 vs observed: 0.5 µg/dL) and local BLL (1.24 vs 1.16 µg/dL). Repeating local BLL simulations with lower Pb concentration in the air or soil based on regulatory guidelines showed a much stronger impact of decreasing soil Pb as compared to air Pb. Concluding, this work shows that soil remediation should be prioritized to lower local children’s BLL. Also, the combined use of case-specific environmental Pb levels and biomonitoring data can increase the level of confidence toward an IEUBK-driven identification of the most effective measure for lowering children’s BLLs, in the ≤2 µg/dL domain.