Performance Analysis and assessment of the airflow interchange system between the mated Space Shuttle Orbiter and International Space Station (ISS) is a vital task to ensure a successful completion of the ISS assembly missions. A multi-module mated air interchange system performance computer model was developed and upgraded for evaluating the atmospheric characteristics within each habitable volume on the Orbiter and all modules of the ISS. The results from this model can be utilized to assess and determine Orbiter's interchange airflow supply capabilities, develop mated air interchange system design limitations and requirements, and predict possible mated air interchange system operating constraints during the assembly missions. The results from this performance model were also used to ensure the air interchange system operation will meet the specific environmental requirements and interface hardware design constraints. The performance analysis and assessment for the ISS assembly mission 5A was selected to show that this model can provide a valuable information for design and operation of the mated air interchange system.