<p>To address the persistent problem of isophorone (IPO) contamination in aqueous environments, a novel composite catalyst consisting of CuO quantum dots (QDs) supported on CeO₂ nanorods was fabricated via a facile deposition–precipitation method, and its performance in activating peroxymonosulfate (PMS) for IPO degradation was systematically investigated. Compared with conventional CuO particles, CuO QDs offer superior electron transport, high specific capacity, and abundant active sites. The synergistic effect between CuO QDs and CeO₂ nanorods further enhances PMS activation efficiency. Over a broad pH range, CuO QDs/CeO₂ exhibits excellent catalytic degradation performance for IPO, achieving a degradation rate of over 94% within 20&#xa0;min. In the presence of CO₃²⁻ and HCO₃⁻ anions, the degradation efficiency can be enhanced to 95.40% and 99.22%, respectively. X-ray photoelectron spectroscopy (XPS) analysis indicated that the Ce⁴⁺/Ce³⁺ redox cycle promoted the Cu²⁺/Cu⁺ redox cycle, generating a bimetallic synergistic effect that maintains a high concentration of oxidizing active species in the system. Quenching experiments and electron spin resonance (ESR) tests showed that in the CuO QDs/CeO₂-activated PMS system, the active species responsible for IPO degradation were mainly hydroxyl radicals (HO•), superoxide radicals (O₂^•−), and singlet oxygen (¹O₂). Additionally, intermediates during IPO degradation were identified by gas chromatography-mass spectrometry (GC–MS), and possible degradation pathways and mechanisms were proposed.</p>