In advanced 20nm and below technology nodes, the mask enhanced error factor (MEEF) plays an important rule due to the request of stable process control and quality of mask manufacture. It provides us an effective parameter to analyze the process window for lithography. In advanced nodes, MEEF criterion becomes more important than previous nodes because very tight process tolerance is requested, especially in OPC and mask capability control. Therefore, we have to do further studies on this topic. In the simple line/trench design layers (for example: Active and poly), the MEEF is easy to be defined because mask bias is isotropic. However, in the complicated two-dimensional (2D) design layers (for example: Contact and Mvia), they are hard to be defined a suitable definition of MEEF. In the first part, we used the global bias to calculate the MEEF on all patterns. It makes calculation easier to compare with other patterns which are different shapes. However, when we inspected the 2D line-end patterns on the wafer, we found the significant differences between the MEEF of wafer data and aerial simulation. In order to clarify this issue, we perform series simulation studies of the line-end MEEF. Then we knew that it came from the different bias strategies. Furthermore, the simulation studies show that the line-end MEEF of non-preferable orientation is very sensitive to mask X/Y ratio bias due to strong OAI optical behavior by the SMO source. As a result, a new point of view of 2D MEEF is suggested according to physical mask CD error measurement data. In this study, we would find a better description of the MEEF than traditional one for lithographic process development on 2D region.