The so-called “in-vessel retention (IVR)” is a severe accident management strategy, which is widely adopted in most advanced nuclear power plants. The IVR mitigation is assumed to be able to arrest the degraded melting core and maintain the structural integrity of reactor pressure vessel (RPV) within a prescribed hour. Essentially, the most dangerous thermal–mechanical loads can be specified as the combination of critical heat flux (CHF) and internal pressure. The CHF is the coolability limits of RPV submerged in water (∼150 °C) and heated internally (∼1327 °C), it results in a sudden transition of boiling crisis from nucleate to film boiling. Accordingly, from a structural integrity perspective, the RPV failure mechanisms span a wide range of structural behaviors, such as melt-through, creep damage, plastic deformation as well as thermal expansion. Furthermore, the geometric discontinuity of RPV created by the local material melting on the inside aggravates the stress concentration. In addition, the internal pressure effect that usually neglected in the traditional concept of IVR is found to be having a significant impact on the total damage evolution, as indicated in the Fukushima accident that a certain pressure (up to 8.0 MPa) still existed inside the RPV. This paper investigates structural behaviors of RPV with the effects of CHF and internal pressure. In achieving this goal, a continuum damage mechanics (CDM) based on the “ductility exhaustion” is adopted for the in-depth analysis.