Persistent contaminants such as polymeric microplastics and cytotoxic pharmaceuticals pose distinct challenges to water treatment systems due to their structural stability and resistance to conventional removal processes. This study investigates two intensified ozone-based oxidation strategies targeting low-density polyethylene (LDPE) and cyclophosphamide (CP) under laboratory-scale conditions. For microplastic degradation, an O₃/UV/US system was developed to enhance ozone activation through combined ultraviolet irradiation and ultrasonic treatment. The synergistic energy input promoted reactive oxygen species formation, resulting in pronounced surface oxidation, functional group modification, and progressive polymer chain scission of LDPE. The carbonyl index of O₃/UV/US-treated LDPE reached 3.84 and 1.32 times higher than those treated with O₃ alone and O₃/US, respectively. Radical identification confirmed the dominant involvement of •OH along with O₂•⁻ and ¹O₂ in driving polymer transformation. Scale-up experiments supported the consistency of batch results, and phytotoxicity assessment using edible seedlings indicated negligible residual effects. For pharmaceutical removal, a hybrid catalytic system (O₃/Ti₃C₂@CF/Al*) integrating Ti₃C₂ MXene immobilized on carbon fiber and metastable aluminum-water clusters was constructed to regulate interfacial ozone activation. The system established a superoxide-dominated oxidation regime (O₂•⁻ > •OH > ¹O₂) driven by electron-transfer-mediated ozone reduction and amplified secondary radical propagation. Complete CP degradation was achieved within 20 min at neutral pH with an observed rate constant of 0.9552 min⁻¹. Transformation product analysis indicated hydroxylation with limited chlorinated intermediates without persistent accumulation, consistent with phytotoxicity results showing no aggravated physiological stress. The immobilized catalyst maintained >90% removal efficiency over five reuse cycles with minor kinetic decline. Multi-criteria comparison demonstrated superior degradation kinetics and removal speed relative to O₃, BDD/BDD, and UV/H₂O₂ systems. Collectively, these findings demonstrate that ozone-based oxidation performance can be effectively intensified through both energy-assisted and material-engineered activation pathways, advancing controllable ozone activation strategies for structurally diverse contaminants in water treatment applications.