A growing interest in dental practice in intranasal anesthesia using tetracaine and oxymetazoline dictates the need for their simultaneous determination in combination drugs and human saliva. Potentiometric multisensory systems based on perfluorosulfonic acid membranes, including polyaniline‐modified ones, were developed for these purposes. A change in the distribution of the sensor sensitivity to the related analytes was achieved by variation of the conditions for concentration polarization at the membrane interface with a studied solution due to a change in the intrapore volume, nature, and availability of the sorption centers, as well as the hydrophilicity of the membrane surface that were specified by the conditions for their synthesis and subsequent hydrothermal treatment. Reversibility of the analyte sorption using the chosen conditions for regeneration provided long‐term stable work of both the sensors and the calibration equations established by multivariate linear regression. The membrane modification promoted their resistance to fouling. The relative errors of the simultaneous tetracaine and oxymetazoline determination in the combination drug solutions were no greater than 7% and 11%, while in the artificial saliva solutions, they were 15% and 17%, respectively, when an array of the cross‐sensitive sensors based on the composite membranes prepared by different methods was used. The analysis errors were reduced to 3%–6% when analyzing the drug and to 0.2%–6% when analyzing the artificial saliva if an array was organized with the sensors based on the membrane with the dopant and the membrane without it, due to the decreasing correlation between their responses.