Display omitted •Catanionic niosomes, composed of cationic and anionic surfactants, are multifunctional carriers for anticancer drugs.•CTAB and SDS were utilized as positively and negatively charged surfactants, respectively.•The behavior of Cabozantinib, an FDA-approved c-Met inhibitor, as the drug sample, was studied in the bilayer.•The influence of cationic/anionic molar ratios on the bilayer features was investigated. Niosomes are adaptable nanocarriers for the delivery and controlled release of anticancer drugs. The addition of ionic surfactants could easily functionalize these carriers. Catanionic niosomes that are comprised of cationic and anionic surfactants are effective drug-delivery vehicles. Here, we aim to evaluate the impact of the cationic/anionic ratio on the noisome characteristics. A novel approach utilizing molecular modeling was utilized to analyze some characteristics of catanionic niosomes, showing great potential as a vehicle for anticancer drugs. The nonionic surfactant SPAN60, along with cholesterol as the stabilizer, was utilized in the study. Moreover, CTAB and SDS were used as positively and negatively charged surfactants, respectively. An FDA-approved c-Met inhibitor, cabozantinib, was selected as the drug. Several significant parameters associated with the cabozantinib molecule and its properties within the bilayer like hydrogen bonding, total energy, radius of gyration (Rgyr), diffusion coefficient, and radial distribution function (RDF). The findings suggest that the cabozantinib’s hydrogen bonding plays a vital role in the drug’s movement through the bilayer. The CTAB-rich niosomes showed a higher number of hydrogen bonds compared to the SDS-rich formulations. The diffusion coefficient was in agreement with the number of H-bonding, and this value increased from 3.12 × 10-12 (m2/s) in CTAB-rich niosome to 7.66 × 10-12 (m2/s) in SDS-rich niosime. The total binding energy between the drug and bilayer components can control drug release. The computational approach could sufficiently describe the influence of cationic/anionic molar ratios on the bilayer features, and the characteristics of catanionic niosomes could be easily adjusted for the controlled release of anticancer drugs.