A novel nanostructured ZnO-Fe3O4/TiO2 composite derived from MIL 125(Ti) was synthesized using mixed solvo-hydrothermal and sol-gel methods for efficient removal of Reactive Blue 21 (RB 21) from aqueous solutions under different conditions. The thermal stability, crystalline structure development, and superparamagnetic properties of the final composite were evaluated by thermogravimetric analysis, X-ray diffraction, and vibrating sample magnetometer instrument. The results approved that the as-synthesized ZnO-Fe3O4/TiO2 possessed a very high thermal stability up to ~ 900°C along with Zn-O, Ti-O, and Fe-O functional groups formation, which endowed superparamagnetic properties to this structure. A significant reduction of surface area from 603.96 (MIL 125(Ti)) to 51.48 m2/g (ZnO-Fe3O4/TiO2) was ascribed to the retailoring in construction, mesoporosity, and pore diameter development with a positive impact on the photocatalytic activities of the final product. The optimum condition with > 99% RB 21 removal was assigned at pH, initial concentration dye, catalyst dosage, and temperature of 2, 50 mg/L, 30 mg/100 mL, and 45°C, respectively. The thermodynamic studies disclosed that the adsorption process was nonspontaneous and endothermic. Furthermore, the synthesized ZnO-Fe3O4/TiO2 composite retained > 95% of its initial removal potential after five successive adsorption/desorption runs. Accordingly, ZnO-Fe3O4/TiO2 can be proposed for the successful removal of RB 21 in the wastewater treatment process.