Rapid progress in the reduction of substrate thickness for silicon-based microelectronics leads to a significant reduction of the device bending stiffness and the need to address its implication for the thermo-mechanical fatigue behavior of metallization layers. Results on 5 µm thick Cu films reveal a strong substrate thickness-dependent microstructural evolution. Substrates with hs = 323 and 220 µm showed that the Cu microstructure exhibits accelerated grain growth and surface roughening. Moreover, curvature-strain data indicates that Stoney’s simplified curvature-stress relation is not valid for thin substrates with regard to the expected strains, but can be addressed using more sophisticated plate bending theories.