In this study, an effective and selective approach for determining methamphetamine by magnetic nanoparticles coated with poly(3-thienylboronic acid) (Fe3O4@P3Th) as a new magnetic solid-phase extraction adsorbent (MSPE) in the biological environment was developed. Synthesis of Fe3O4@P3Th magnetic nanoparticles (MNPs) was approved by Fourier transform infrared (FT-IR) spectroscopy, vibrating sample magnetometer (VSM), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), powder X-ray diffraction (XRD), and Elemental mapping and EDX analysis. The main factors influencing extraction efficiency, including the amount of nano adsorbent (20–60 mg), type and amount of organic extraction solvent (water-ethanol %), temperature (25–35 °C), pH (3–9), and extraction time (5–210 min), were investigated and optimized using a Support-vector machine. The low mean squared error (Mse) and high correlation coefficient (close to 1) for train, validation, and test data indicate successful and accurate machine backup vector predictions. Adsorption efficiency of 88.9 ± 0.42% was obtained for nano adsorbent in ethanol at the optimal condition (pH: 7, temperature: 35 °C, time: 210 min, and for 60 mg of nano adsorbent). Methamphetamine exhibited good linearity in the concentration range from 100 to 5000 ng/mL under optimal extraction conditions. The results of adsorption showed high chemical stability and adsorption capacity of nano adsorbents due to the presence of P3Th. Therefore, Fe3O4@P3Th magnetic nanoparticles (MNPs) could be used as a new MSPE in clinical and forensic laboratories to determine the materials used in the urinary environment.