A system and method for estimating image intensity bias and segmentation tissues is presented. The system and method includes obtaining a first image data set and at least a second image data set, wherein the first and second image data sets are representative of an anatomical region in a subject of interest. Furthermore, the system and method includes generating a baseline bias map by processing the first image data set. The system and method also includes determining a baseline body mask by processing the second image data set. In addition, the system and method includes estimating a bias map corresponding to a sub-region in the anatomical region based on the baseline body mask. Moreover, the system and method includes segmenting one or more tissues in the anatomical region based on the bias map.