Stressors have been used since 90 nm technology to improve device performance to overcome the limitations of scaling. The stressors, including,- CPEN, TPEN, SMT, and e-SiGe to improve NMOS and PMOS drive current exhibit proximity dependence. In addition, unintentional stressors such as STI edge proximity introduce additional layout dependencies. Two devices with the same L and W can have significantly different drive strength depending on their surroundings. There have been limited studies to optimize the design layout to reduce the layout-dependent stress degradation. Circuit and layout designers have few tools they can use to quickly and effectively optimize the layout to reduce device degradation due to layout-dependent stress effects. In this paper, we present a comprehensive set of CAD utilities, and stress-related layout guidelines to optimize the layout for full custom macros to reduce the layout-dependent stress effects prior to doing full timing characterization, including stress effects.