The increased presence of toxic chemicals in aquatic matrices and their associated health effects raise the need for more effective treatment technologies. The application of Fe(VI), an advanced oxidation treatment agent with disinfecting and coagulating capabilities, is limited by Fe(VI) aqueous instability. Our previous study proposed an Fe(VI)-coated sand media to overcome this constraint and demonstrated that Fe(VI)-coated sand was an effective medium for the treatment of phenolic compounds. In this study, we assessed the potential of the media for treatment of acetaminophen (ACM), benzotriazole (BZT), sulfamethoxazole (SMX), copper (Cu), lead (Pb), and zinc (Zn)-common contaminants found in wastewater effluents-in ultrapure and synthetic wastewater effluent. Fe(VI)-coated sand reactivity was influenced by the solution pH and aqueous chemistry. For example, the removal of Pb improved by 39% in the presence of trace organics, indicating that trace metal removal was enhanced by Fe(III) phases formed during Fe(VI) reactions with trace organics. While oxidation of trace organic compounds increased as pH decreased, trace metal sorption was more favorable at higher pH (i.e., pH 8 and 9). The oxidation efficiency of trace organics by the media was the highest for ACM and SMX while BZT degradation was limited due to formation of Cu-BZT complexes. Batch tests in synthetic wastewater effluent revealed that the presence of divalent cations (i.e., Ca2+ and Mg2+) can catalyze Fe(VI) self-decay and promote Fe(III) production and subsequent trace metal removal; however, oxidation of trace organics was hindered in this matrix. This study highlights the potential for Fe(VI)-coated sand application for the treatment of complex matrices more representative of natural and engineered aquatic systems.