Abstract: Methods and systems for using dynamic data-driven detector tuning to investigate a sample with a charged particle microscopy system are disclosed herein. Methods and systems according to the present disclosure include acquiring sample data for a region of interest on the sample, and then determining one or more materials present in the region of interest. Once the materials are identified, a differentiation detector window is identified for the one or more materials, and the detector settings of a detector are adjusted such that the detector obtains information within the differentiation detector window. Thus, as the sample is subsequently scanned, the detector obtains an optimal range of information that is allows for efficient differentiation among the one or more materials.