Bortezomib (BTZ) and dasatinib (DA) are two substantial anti-cancer agents with side effects on the human body. In this research, we fabricated a novel electrochemical sensor modified by CuFe2O4/ SmVO4 nanocomposite and 1-ethyl-3-methylimidazolium chloride (1E3MC) as an ionic liquid (IL) ( CuFe2O4/SmVO4/IL/CPE) for coinciding investigation of BTZ and DA for the first time. The CuFe2O4/ SmVO4 synthesized were determined and certified through field-emission scanning electron microscopy (FE-SEM), energy diffraction X-ray (EDX), and X-ray diffraction (XRD). The capability of the sensor was investigated by different electrochemical techniques such as cyclic voltammetry (CV), chronoamperometry (CHA), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). The attained data showed that the oxidation signal of bortezomib and dasatinib promoted as an innovative electrochemical sensor. After optimization of the conditions using this sensor at pH 7.0, the oxidation signal of bortezomib and dasatinib showed to be linear with drug concentrations in the range of 0.09–90 μM and 100–500 μM with a detection limit of 5.4 nM and 7.0 μM, respectively, using differential pulse voltammetry method. The values of D and electro-transfer coefficient (α) achieved 2.5 × 10− 5 cm2 s− 1 and 0.99, respectively. The proposed electrochemical sensor exhibited acceptable selectivity and sensitivity for simultaneous detection of bortezomib and dasatinib in pharmaceutical and biological samples.