This contribution deals with a Discrete Element Method (DEM) framework to simulate and investigate the mechanisms leading to the failure of plasma-sprayed Thermal Barrier Coating (TBC) systems. A hybrid lattice-particle approach is proposed to determine residual stress fields induced by the Coefficient of Thermal Expansion (CTE) mismatch during a cooling-down phase. Besides, this is combined with a mixed-mode Cohesive Zone Model (CZM) to simulate interface delamination, and the Removed Discrete Element Failure (RDEF) criterion to model crack initiation and propagation in TBC system. The context of a unit cell model with a perfectly sinusoidal interface profile is first investigated to highlight the suitability of the proposed DEM-based approach in terms of stress fields and failure process. The case of a real microstructure reproduced by the image processing is then discussed. This underlines the effect of porosity and surface asperities on the failure mechanisms. Results exhibit the potential of the proposed DEM approach to model complex cracks phenomena occurring in TBC systems under thermal loading.