In this work, a novel flexible electrochemical sensor was successfully developed for the simultaneous determination of p-aminophenol and acetaminophen. The sensor is composed of a methanesulfonic acid-treated poly(3,4-ethylenedioxythiophene)/poly (styrenesulfonic acid) film on a poly (ethylene terephthalate) substrate, which has been modified using a zinc oxide-doped tin oxide heterojunction applied through drop-coating (C-ZnO/SnO2-PEDOT/PET). The oxygen vacancies resulting from zinc oxide-doped tin oxide heterojunctions within highly conductive metal oxide nanomaterials enhance mass transfer and synergize seamlessly with methanesulfonic acid-treated electrically conductive dielectric PEDOT/PET films, leading to a substantial improvement in electrochemical activity. Under the optimal conditions, a wider linear range and lower detection limits were shown for para-aminophenol (2-511μM, LOD=0.437μM) and acetaminophen (2-591μM, LOD=0.562μM). In addition, the sensors demonstrated high accuracy in detecting para-aminophenol and acetaminophen in real samples, with recoveries of 99.36%-99.60% and 97.56%-99.80%, respectively. Furthermore, the flexible sensors maintained a superior electrochemical response when detecting para-aminophenol and acetaminophen at different bending angles, with relative standard deviations of 0.62% and 1.68%, respectively. These findings suggest potential applications for the development of wearable sensors in the future.