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A physical model and a simulation algorithm are used to predict an electromigration-(EM-) induced void nucleation and growth in dual-inlaid copper interconnect. Incorporation of all important atom migration driving forces into the mass balance equation and its solution together with solution of the coupled electromagnetics, heat transfer, and elasticity problems allows to simulate EM-induced degradation in a variety of dual-inlaid copper interconnect segments characterized by different dominant channels for mass transport. The interface bonding strengths, significantly influencing the interface diffusivity and consequently the mass transport along interfaces, 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 results of the numerical simulation have been proven experimentally by the EM degradation studies on the fully embedded dual-inlaid copper interconnect test structures. EM-induced void formation, movement, and growth in a copper interconnect were continuously monitored in an in situ scanning electron microscopy experiment. The correspondence between simulation results and experimental data indicates the applicability of the developed model for optimization of the physical and electrical design rules. Simulation-based optimization of the interconnect architecture, segment geometry, material properties, and some of the process parameters can generate on-chip interconnect systems with a high immunity to EM-induced failures.