This work addresses in-situ synergistic irradiation and thermomechanical loading of nuclear reactor components by linking new mechanistic understanding with crystal plasticity finite element modelling to describe the formation and thermal and mechanical annihilation of dislocation loops. A model of pressurised reactor cladding is constructed to extract realistic boundary conditions for crystal plasticity microstructural sub-modelling. Thermomechanical loads are applied to the sub-model to investigate (i) the unirradiated state, (ii) synergistic coupling of irradiation damage and thermal annihilation of dislocation loops, (iii) synergistic coupling of irradiation damage without thermal annihilation of dislocation loops, and (iv) a post-irradiated state. Results demonstrate that the synergistic coupling of irradiation damage and thermomechanical loads leads to the early onset of plasticity, which is exacerbated by the thermal annihilation of dislocations, while the post-irradiated case remains predominantly elastic due to substantial irradiation hardening. It is shown that full synergistic coupling leads to localisation of quantities linked with crack nucleation including geometrically necessary dislocations and stress.