The work was especially focused on confirming a brilliant connection of molecular modeling application as a modern computational chemistry and practical application to design, develop and characterize electrochemical sensors for determination of drugs. Here, for the first time, three modified polyvinyl chloride membrane sensors were developed for the electrochemical determination of solifenacin succinate in pure and pharmaceutical dosage form. These sensors were modified using alpha (α), beta (β) and gamma (γ) cyclodextrin (CD) ionophores and each membrane contained dioctyl phthalate as a plasticizer. The α, β and γ-modified sensors showed stable and rapid near-Nernstian responses of 48.92, 57.05 and 52.37, respectively, over a solifenacin concentration range of (1 × 10−2–5 × 10−5 mol L−1) and a limit of detection 2.5 × 10−5, 7.9 × 10−6 and 3.9 × 10−5 mol L−1, respectively. Molecular modeling and docking techniques were used to study the nature of the binding between the drug and ionophore molecules. Also, to assist the interpretation of the obtained results and to compare the performance of different sensors. The proposed electrodes were successfully applied for its determination in the pharmaceutical dosage form.