We present lithospheric strength profiles calculated for a transect running from the Island of Corsica, in the west, to the Apennine foredeep in the east. Strength profiles are constructed at locations selected on the basis of the availability of seismic, heat flow, gravity data and earthquake foci distribution. Rheological modelling points to the presence of strong lateral variations in the thermo-mechanical state of the lithosphere. The Tyrrhenian-Tuscany area has a low rigidity in relation with the intense stretching active from the Early Miocene, and with very high heat flow associated with asthenospheric rise. On the contrary, hinterland (Corsica) and Apenninic foreland areas (Adriatic area) show a higher level of lithospheric strength. Effective elastic thickness estimates confirm this scenario, exhibiting a strong reduction from the northern Tyrrhenian to the inner Apennines and then an abrupt increase in correspondence of the Adriatic plate. The distribution of earthquake focal depths confirms the presence of a brittle rheology in the first kilometres of the crust in the Tuscany area, whereas close to the plate boundary much lower thermal gradients, partly induced by the westward-plunging Adriatic plate, enable seismic activity to occur at larger depths.