Combining global experience, comprehensive aging knowledge, and predictive methodologies provides ideal prerequisites for the long-term operation strategy (LTO) of a nuclear power plant (NPP). Applying management strategies with an understanding of the ways in which structures relevant for the plant safety perform and interact in their operating environments is of meaningful importance for operating the plant beyond its originally licensed service life. In performing aging studies on the nuclear systems, structure, and components (SSCs), the results are crucial for demonstrating the safety and reliability of the NPP beyond 30 years of nominal operation. In this study, the synergistic effect of a creep mechanism with the alteration suffered by piping material is analyzed by means of MSC©MARC finite element code. Nonlinear analyses were performed to calculate the effects of the long operational period on a primary pipe, assess its degradation, and determine its residual functionality. In these analyses, both homogeneous and inhomogeneous pipe wall thinning are considered, as well as the operating or expected thermal–mechanical loads. The obtained results indicate that thermo–mechanical loads are responsible for pipe deformation, which develops and increases as the transient progresses. Furthermore, an excessive (general or local) wall thinning may determine a dimensional change of the pipe, even causing bending or buckling.