Cosmic Ray Energetics and Mass for the International Space Station (ISS-CREAM) is designed to directly measure the energy spectra of high-energy cosmic rays, encompassing proton to iron nuclei, over the energy range from 1012 to 1015 eV [1]. The capability to measure an extended energy range enables us to probe the origin and acceleration mechanisms of cosmic rays. The ISS-CREAM instrument is configured with the balloon-borne CREAM calorimeter (CAL) for energy measurements and four layers of a finely segmented Silicon Charge Detector (SCD) for charge measurements. In addition, two new compact detectors have been developed for electron/proton separation: Top and Bottom scintillator-based counting detectors (TCD/BCD) and a boronated scintillator detector (BSD). Simulations use the GEANT3 package [2] with the FLUKA hadronic model [3]. An isotropic event generator was developed for the ISS-CREAM geometry with particles incident from the upper hemisphere. We will present simulation results regarding ISS-CREAM performance, including trigger rates, energy resolution, energy response, tracking resolution, charge efficiency, etc.