Ultrasound-assisted solid-phase microextraction (SPME) by a functionalized high surface area ZnO nanoparticle (NP)-based molecularly imprinted polymer (MIP) followed by UV-Vis spectrophotometry was described as a selective, economic and rapid technique which was established for the extraction and preconcentration of meloxicam (MEL) in water media and plasma. ZnO@MIP-NPs were fabricated via a surface molecular imprinting polymerization method, and subsequently, were characterized by FT-IR, SEM and DLS techniques. The operational variables such as solution pH, dosage of MIP, type and volume of eluent, and adsorption and desorption time were investigated and optimized. After optimization, kinetic and isotherm models for the adsorption of MEL onto ZnO-NPs@MEL-MIP were assessed and fitted. Under the optimum experimental conditions, the calibration curve exhibited a linear range of 0.1–10.0 mg L⁻¹ of the MEL concentration with a detection limit of 0.008 mg L⁻¹. The relative standard deviation for the analyte was found to be lower than 2.81%. The ZnO-NPs@MEL-MIP adsorption capacity was found to be 53.47 mg g⁻¹. The preconcentration factor was found to be 25. The results showed that the prepared sorbent could be successfully applied for the determination of MEL in water and plasma samples.