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The rapidly evolving telecommunications market has led to the need for advanced RF circuits. Complex multi-band/multi-mode RF designs require accurate prediction early in the design schedule and time-to-market pressures require that design iterations be kept to a minimum. This paper presents a layout-level, multi-domain DFM methodology and yield optimization technique for embedded RF circuits for SiP-based wireless applications. The proposed concept consists of layout- level statistical diagnosis and yield optimization. The statistical analysis takes into account the effect of the thermo-mechanical stress and the process variations that are incurred in batch fabrication. The results show good correlation with measurement/electromagnetic (EM) data.