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Physically based simulations are used to predict an electromigration (EM)-induced void nucleation and growth in dual-inlaid copper interconnects. Incorporation of all important atom migration driving forces into the mass balance equation and its solution together with the solution of the coupled electromagnetics, heat transfer, and elasticity problems allows one to simulate EM-induced degradation in a variety of interconnect segments characterized by different dominant channels for mass transport. The existence of the weak interfaces between copper and diffusion barriers results in different EM-induced degradation pictures in aluminum and copper interconnects. The interface bonding strengths, significantly influencing the interface diffusivity and, consequently, the mass transport along interfaces in the case of copper interconnect, result in completely different degradation and failure pictures for the weak and strengthened copper/capping layer interfaces. Strengthening of the top interface of inlaid copper interconnect metal line is a promising way to prolong the EM lifetime. The correspondence between simulation results and experimental data indicates the applicability of the developed model for the optimization of the physical and electrical design rules. By varying the interconnect architecture, segment geometry, material properties, and some of the process parameters, users will be in a position to generate on-chip interconnect systems with high immunity to EM-induced failures.