<p>The composite materials of Mn oxide nanowires and ZIF-8 (Mn_xO_y NWs@ZIF-8-NF and ZIF-8@Mn_xO_y NWs-TH) with controllable sizes and morphologies (nanoflower and Tanghulu-like) were successfully synthesized using different solvents (water and dimethylformamide (DMF) under mild reaction conditions. The systematic investigation was conducted to evaluate the effects of key synthesis parameters, including precursor concentration, metal-to-ligand ratio, temperature, and time, on the microstructure and crystalline morphology of the materials. Furthermore, the synthesis mechanisms of the materials in different solvents (water and DMF) were explored, revealing the influence of solvent molecules on their crystal growth processes. The prepared materials serve as “tandem enzymes” (a single nanozyme composite can perform multiple or sequential catalytic reactions), possessing multiple enzyme-like activities (hydrolase- and oxidase (OXD)-like activities). Kinetic studies indicate that the Mn_xO_y NWs@ZIF-8-NF composite exhibits excellent hydrolase-like catalytic activity, characterized by the high substrate affinity and maximum reaction rate (<i>K</i>_m: 0.01493 mM, <i>V</i>_max: 161.42 × 10^–8 M/s). Moreover, Mn_xO_y NWs@ZIF-8-NF exhibits high specificity and interference-resistance in fluorescent detection of glucose oxidase (GOX) based on its hydrolase and OXD-like activities. In short, this work investigates the role of solvents as one aspect of tailoring material properties, contributing to the development of advanced functional materials and offering a methodological reference for GOX detection.</p> Graphical Abstract <p></p>