This paper investigates variability across multiple lithographic domains, as experienced in typical manufacturing environments, and assesses the impact on achievable post-OPC image fidelity and CD control. Across scanner field and tool-tool effects are considered, and a distinction is made between systematic phenomena, which typically manifest within chip, and random fluctuations, which predominantly impact chip-to-chip mean distributions. The paper will outline which lithographic parameters can effectively be accounted for in OPC models, and over what temporal/spatial extents. The non-correctable phenomena assessed include misalignment, projection optic aberrations, illumination source profile, mask CD, focus and exposure dose variation, and flare. Specific analyses are applied to the case of gate edge placement error (EPE) control as a function of these manufacturing variables. Recommendations are made for "field-aware" metrology sample plans during model creation, such that globally optimized models can be realized. With knowledge of manufacturing input parameter variation, CalibreTM enables a detailed understanding of realistic post-OPC CD control, and can guide judicious product metrology sampling and specifications. It is highlighted that even for the case of a "perfect" OPC model, the post-OPC CD variation within chip can still be substantial, due to manufacturing variability.