Focused ion beam (FIB) instruments have recently started to be seen in applications to organic materials such as polymers and biological samples. FIB provides a novel tool for sectioning biological samples for electron microscope based imaging or microfabrication with environment friendly materials. The modeling of nano/micro scale geometry accurately sculptured by FIB milling is crucial for generating the milling plan and process control, and for computer simulation based prediction and visualization of the milled geometry. However, modeling of the milled geometry on compound materials, especially for high aspect ratio feature, is still difficult due to the complexity of target material, as well as multiple physical and chemical interactions involved. In this study, a comprehensive model of ion milling with organic targets is presented to address the challenges in using a simulation based approach. At each discrete point of the milled front, the depth is the dynamic result of aggregate interactions from neighboring areas, including physical sputtering and chemical reactions. Instead of determining the exact interactions, the parameters of the proposed model are estimated by studying a number of preliminary milling results followed by a nonlinear optimization model. This platform has been validated by milling different features on water ice in a cryogenic environment, and the simulation and experiment results show great consistency. With the proliferation of nanotechnology in biomedical and biomaterial domains, the proposed approach is expected to be a flexible tool for various applications involving novel and heterogeneous biological targets.