2K injection moulding is an important process in polymer processing, enabling the combination of different polymers. The authors developed a process which makes it possible to combine thermoset rubbers and thermoplastics by 2K injection moulding. The moulds used for this specific material combination are equipped with thermally separated mould cavities, required to overcome the problem of the conflicting mould temperatures. In previous studies, the influence of the process parameters on the adhesion strength was investigated. It was found that the mould temperature was by far the most important parameter. However, the obtained adhesion strength not only depends on the used process settings but also on the combination of the specific thermoplastic and thermoset rubber. Since the adhesion strength also depends on the material combination, there is a need to predict the compatibility between a rubber and a thermoplastic. In this study, the wetting behaviour of 5 different thermoplastics on 3 rubber substrates was used to predict their compatibility. Two types of wetting experiments have been performed: (i) direct contact angle measurements of molten thermoplastics on rubber substrates, and (ii) calculation of the wetting parameters based on the surface energies and components for both materials in solid state. For the contact angle measurements of molten polymers on the thermoset rubber substrates, it was observed that the EPDM rubbers were best wetted by PP and PE while the NBR rubber was best wetted by PC. The wetting parameters however, predicted a good wetting behaviour for PP on each of the rubber substrates. The subsequent two-component injection moulding tests indicate that it was possible to combine EPDM only with PE and PP while it was only possible to combine PC with NBR. Therefore, there is a good agreement between the 2K injection moulding tests and the results achieved with the direct contact angle measurements of molten thermoplastics.