At domestic ports and airports, radiation portal monitors (RPMs) have been installed and operated for detection of illegal radioactive materials in cargo containers. In RPM operation, although the alarm level of the RPM is set based on the background count, measured before the cargo container passes through the RPM, suppression of the background count occurs due to shielding by the cargo container and its contents. In this study, we evaluated, using Monte Carlo simulations, background-count variations caused by various conditions of cargo containers and their contents. To that end, the experimental RPM at the Port of Busan in South Korea and a 40 ft cargo container, the most commonly used type in South Korea, were precisely modeled. In order to verify the simulation models, the simulated data on the background count for the empty container were compared with the measured data, as recorded at 0.2-s intervals during container passes through the RPM. When the empty container passed through the RPM, the average background count decreased by approximately 20%–30% with a consistent tendency. It was found that the degree and shape of background suppression varied depending on the cargo conditions. For example, for various cargoes (i.e., potassium chloride, slag powder, and zircon), as the vertical loading increased, the background count varied by approximately 50%–60% on average, and by up to 74% in comparison to the time before the container entered the RPM. The present findings will contribute to the optimization of site-specific alarm criteria for RPM by better enabling realistic estimation of background variation for various factors.