In this study, the synthesis and properties of a selective electrochemical sensor for the determination of osimertinib (OSIM) as an anticancer drug using the bimetal-organic framework (MOF) were reported. Herein, MOF based on nickel/manganese (Ni/Mn-MOFs) was successfully created using the solvothermal method and applied for the amperometric detection of OSIM. Then, Ni/Mn-MOF was analyzed through a field emission scanning electron microscope (FE-SEM) and X-ray diffraction (XRD). The electrocatalytic performance of the introduced MOF is used in the electrochemical determination of the OSIM drug. The synthesized MOF leads to a noticeable improvement in the electrochemical performance which is ascribed to the many electrocatalytic sites, wide electrode–electrolyte contact area, and excellent electrical conductivity. This is the first study on the use of Ni/Mn-MOF to detect of OSIM. The Ni/Mn-MOF modified glassy carbon electrode (Ni/Mn-MOF/GCE) exhibited a good linear range from 0.5 to 800 μM and 800 to 1800 μM with a low detection limit (LOD) as 0.16 μM. In addition, the proposed sensor possessed good anti-interference properties, repeatability, stability, and reproducibility. The mentioned substrate to detect OSIM in the samples of blood serum was successfully applied. This research displays that MOFs are reliable materials for designing effective electrochemical sensors to detect drugs easily. The existing research results provide insights into the promotion and development of the bimetal-organic framework in the field of electrochemical applications and promising for usage in other electrochemical studies.