In this work, we have investigated the mechanical properties of Cu/Ta, Ag/Cu and Ag/Nb multilayers with different heterogeneous interfaces. The results suggest that when individual layer thickness(h) is larger than 5–10 nm, the hardness/strength of three different multilayer systems has the similar length scale effect with decreasing layer thickness,while when h B 5 nm, the three multilayer systems show remarkably different plastic deformation behaviors. The strength curves exhibit the variation trends of unchanging, softening and increasing corresponding to Cu/Ta, Ag/Cu and Ag/Nb multilayers, respectively. The microstructure analysis shows that three kinds of multilayers have totally different interfacial structures, which lead to the different strengthening or softening mechanisms.