A new methodology to quantify the sensitivity and resolution of infrared spectroscopic ellipsometry (IRSE) measurements was developed for probing the depth profile of composition in thin polymer films. A multilayer system comprised of sub-100 nm films of poly(4-hydroxystyrene) on top of poly (methyladamantyl methacrylate) was used as a model test structure for our IRSE measurements of bilayer film thickness and composition profile. The IRSE results are further validated by comparing to high-resolution neutron reflectivity results also from these samples. We demonstrated that the substrate type, incident angle, and specific spectral band regions strongly influence the sensitivity of IRSE; a judicious choice of measurement variables and infrared spectral regions can substantially improve the measurement in terms of sensitivity. Most strikingly, an incidence at the Brewster angle of the substrate does not lend to the maximum sensitivity. Discussions of the origin of these findings and metrics are provided.