This study presents a novel approach the selective determination of Osimertinib (OSIM) using a molecularly imprinted polymer (MIP) based on the electropolymerization strategy. The MIP was immobilized on the surface of a glassy carbon electrode (GCE), serving as the working electrode, through the electropolymerization of monomers such as resorcinol, ortho-aminophenol (o-AP), and the OSIM analyte. For the first time, an electrochemical sensor incorporating a MIP was specifically developed for OSIM detection. The modified electrode was characterized using atomic force microscopy (AFM), scanning electron microscopy (SEM), fourier-transform infrared spectroscopy (FT-IR), differential pulse voltammetry (DPV), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). The proposed sensor demonstrated excellent reproducibility, selectivity, stability, and repeatability. The MIP/GCE provided a linear range from 0.5 to 1000 µM with a detection limit (LOD) of 0.17 µM. Validation was performed using high-performance liquid chromatography (HPLC) as a standard method for determining OSIM in serum sample.