With the ever shrinking semiconductor device features coupled with the increasing circuit density, optical level fault localization techniques such as Photon Emission Microscopy (PEM), Laser Signal Injection Microscopy (LSIM) and Thermal Hotspot Localization (THS) can only get you so far due to these limitations: magnification, spot size and drop in detection sensitive at higher magnification. Using a 100x objective can put you in the ball park. Test data such as ATE & ATPG can point you to a specific block of circuitry but still far from defect localization. With in-SEM fault isolation and localization techniques such as Voltage Contrast (VC), Electron Beam Induced/Absorb Current (EBIC/EBAC) and Resistive Contrast Imaging (RCI), the nano-scale defect can be further localized due to the advantage of the magnification and spot size. This paper offers the combined techniques of optical level fault localization (PEM, LSIM & THS) and in- SEM or E-beam techniques (VC, EBAC, RCI) to successfully perform fault localization when challenged with the above scenarios.