The compounding of polymeric materials frequently requires the incorporation of solid filler particles in order to enhance the mechanical properties of the final product. Most of the fillers exist in the form of large agglomerates which, during the mixing process, are broken down into smaller fragments and uniformly distributed into the matrix. Previous research has generally focused on the investigation of the flow field in the mixing equipment and only few attempts have been made in the analysis of the breakup behaviour of the agglomerates, with most of them adopting severe simplifications either on the flow field or on the aggregate morphology. In this work we present a numerical approach able to investigate accurately the dynamics of the process. The method is based on a combination of Computational Fluid Dynamics (CFD) and Discrete Element Method (DEM) simulations. CFD simulations are carried out to compute the flow field inside a typical internal mixer; during the simulation, the agglomerates are treated as tracer particles, whose trajectories are recorded together with the viscous stress experienced during the motion. This piece of information is then used by a DEM model, built in the framework of Stokesian Dynamics; at this stage the disordered structure of the agglomerates is modelled in detail and the DEM returns the normal force acting on each single monomer-monomer contact. From this information the occurrence of breakup can be readily determined by comparing the tensile force with the critical pull-off force required to break the contact. To our knowledge this is the first study addressing jointly the role that the flow field and the agglomerate structure plays in a compounding operation. The project leading to this application has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 760907.