The Tertiary tectonic evolution of the Central Mediterranean has been relatively well constrained by abundant geological data. Yet, several uncertainties persist about the mechanisms that led to the present‐day surface morphology and deep slab geometry. Here, we combine geodynamic and seismological numerical modeling techniques to reproduce the recent large‐scale evolution of the Central Mediterranean and the associated strain‐induced upper mantle fabrics and seismic anisotropy. 3D thermo‐mechanical subduction models were designed and calibrated according to paleogeographic‐tectonic reconstructions and seismological observations available in the literature. It is found that, although the opening of back‐arc extensional basins in response to the retreat of the Ionian slab is a common feature in all models, structural heterogeneities within the Adria plate and/or the geometry of its Tyrrhenian passive margin profoundly impact on the segmentation of the subducting slab and the amount of Ionian trench retreat. More, in general, this study highlights the importance of coupling geodynamic and seismological modeling to better constrain the tectonic evolution of complex convergent margins such as the Central Mediterranean.