One of the major challenges in the semiconductor industry is to measure the three-dimensional (3D) profile of objects with large step height (>100 µm), as well as nanometer-level surface profiles. In this work, a novel technique called region-based transport of intensity equation (R-TIE) is explored to measure both large step heights as well as local surface profiles with nanometer resolution. The key factors of the R-TIE are the use of composite image segmentation, transport of intensity equation (TIE), and a smart imaging system. The imaging system incorporates an electrically tunable lens to record objects at different focus positions with large field of view, high speed, and no mechanical moving parts. The TIE part of the system allows for nanometer height measurement at areas of interest. We demonstrate the basic principle and feasibility of the proposed method by experimentally measuring different stepped specimens.