A typical photovoltaic (PV) module is composed of different layers bonded together, each with a different material and thus, a different coefficient of thermal expansion (CTE). While under operation, it is subjected to thermal loads due to continuous temperature variations. The CTE mismatch induces thermo-mechanical stresses, whose cyclic nature causes fatigue failure. Due to their relative small size, the copper interconnects are one of the most vulnerable constituents. In this work, the finite element (FE) analysis has been used to calculate these thermal stress/strain variations. To make the simulations more reliable, well-known material models have been adopted from the literature and used for each constituent of the PV module. Furthermore, to reduce computational time and complexity, a simplified modeling approach has been proposed in this work. In this approach, a 2-D FE global model was first used to identify the region that undergoes maximum strain. Then a 3-D FE local model was used for that particular region only. This approach helps calculate the maximum stress/strain variations. Thus, using the proposed modeling approach coupled with a fatigue criterion, one can calculate the fatigue life of the PV module, while significantly reducing the computational time. The initial conditions, in terms of residual stresses, due to the lamination process for the fabrications of the PV module are also accounted for in our approach. We applied our approach to silicon-based PV module under desert weather conditions of Doha (Qatar) and the results show a reduced life compared to the one provided by the manufacturer.