Contamination of surface and groundwater resources with heavy metals such as arsenic and copper is one of the most significant environmental challenges associated with mining industries. Acid mine drainage (AMD) from the concentration and smelting plants of the Sarcheshmeh Copper Complex is a prominent example of such pollutants, and potential and appropriate strategies are needed to mitigate its adverse effects. One novel and environmentally friendly method is phytoremediation using hyperaccumulator plants. In this study, the effects of titanium dioxide (TiO₂) nanoparticles and EDTA on enhancing the phytoremediation of arsenic and copper by C. alternifolius were investigated under laboratory conditions. Seven treatments, including irrigation with tap water (control), irrigation with AMD, irrigation with AMD supplemented with EDTA, irrigation with AMD amended with TiO₂ nanoparticles at concentrations of 200 and 300 mg kg⁻¹, and combinations of TiO₂ nanoparticles with EDTA, were evaluated. The maximum uptake rates of arsenic and copper were estimated at 989.6 and 720.7 kg ha⁻¹ yr⁻¹, respectively, corresponding to removal efficiencies of 58.7% and 50.8% in the TiO₂ nanoparticle treatments. The application of EDTA significantly reduced arsenic uptake by the plants. Based on the bioconcentration factor (BF), C. alternifolius showed a high capacity for copper accumulation but not for arsenic. These findings indicate that the use of C. alternifolius, especially in combination with modern nanotechnology, could be a promising approach to improving management and reducing pollution from industrial effluents.