The numerical simulation of rocket engine thrust chambers is very challenging as several damaging phenomena, such as plasticity, low-cycle-fatigue (LCF) and creep occur during its service life. The possibility of simulating the thermostructural behavior of the engine, by means of non-linear finite element analyses, allows the engineers to guarantee the structural safety of the structure. This document reports the numerical simulations developed with the aim of predicting the thermostructural behaviour and the service life of the thrust chamber of a liquid-propellant rocket engine. The work represents a step ahead of previous researches by the authors, with particular reference to the addition of the Smith-Watson-Topper (SWT) fatigue criterion, and to the implementation of a sub-modelling technique, for a more accurate assessment of the most critical section of the component. It was found that the equivalent plastic strains in the most critical nodes obtained through the sub-modelling technique were about 20% lower than those calculated without sub-modelling. Consistently with experimental tests from literature conducted on similar geometries, the most critical areas resulted to be on the internal surface of the chamber. The analyses demonstrated that the LCF damaging contribution was significant, with a life prediction for the thrust chamber of about 3400 cycles.