Protective compartments are typically used to protect some specific structures from internal explosions, such as industrial buildings that contain devices that may explode in certain circumstances. This research investigates how the response of reinforced concrete (RC) compartment structures subjected to internal blast loads are affected by the following aspects: introduction of material nonlinearity in the analysis, reinforcement ratio, and aspect ratio of the compartment. To achieve this goal, a calibrated and sophisticated FE numerical model is introduced, and a parametric study for the intended aspects is carried out. A discussion of the results and conclusions are offered, which show the role of each aspect in the dynamic performance of the compartment structures. The main conclusions are as follows: introduction of material nonlinearity in this type of analysis and for these structures is very important and significant in obtaining accurate outputs that are similar to actual behavior; the reinforcement ratio has a significant effect on the response and its effect varies depending on the thickness of the compartment; in general, increasing the reinforcement ratio enhances the behavior and reduces the stresses in the compartment; and the aspect ratio of the compartment does not show a clear pattern on the response of such structures under internal blast loads.