In the past two decades, the radioactive particle tracking (RPT) measurement technique has been proven to visualize flow fields of most multiphase flow systems of industrial interest. The accuracy of RPT, and hence the data obtained, depend largely on the calibration process, which stands here as a basis for two subsequent processes: tracking and reconstruction. However, limitations in the RPT calibration process can be found in different experimental constrains and in assumptions made in the classical Monte Carlo approach used to simulate number of counts received by the detectors. Therefore, in this work, we applied a GEANT4-based Monte Carlo code to simulate the RPT calibration process for an investigated multiphase flow system (i.e., gas–liquid bubble column). The GEANT4 code was performed to simulate the number of counts received by 28 scintillation detectors for 931 known tracer positions while capturing all the types of photon interaction and overcoming solids' angle limitations in classical approaches. The results of the simulation were validated against experimental data obtained using an automated RPT calibration device. The results showed a good agreement between the simulated and experimental counts, where the maximum absolute average relative deviation detected was about 5%. The GEANT4 model typically predicted the number of counts received by all the detectors; however, it over-estimated the counts when the number of primary events applied in the model was not the optimal.