Mask manufacturers will be impacted by two significant technology requirements at 22 nm and below: the first is the more extensive use of resolution enhancement technologies (RET), such as aggressive optical proximity correction (OPC), inverse lithography technology (ILT), and source mask optimization (SMO); the second is the extreme ultraviolet (EUV) technology. Both will create difficulties for mask inspection, defect disposition, metrology, review, and repair. For example, the use of ILT and SMO significantly increases mask complexity, making mask defect disposition more challenging than ever. The EUV actinic inspection and AIMS™ will not be available for at least a few years, which make the EUV defect inspection and disposition more difficult, particularly regarding multilayer defects. Computational metrology and inspection (CMI), which has broad applications in mask inspection, metrology, review, and repair, has become essential to fill this technology gap. In this paper, several such CMI applications are presented and discussed.