Mixed-matrix membranes (MMMs), combining mechanical/separation properties and processability of different materials, have been considered as promising materials in tackling challenging gas separation problems such as carbon dioxide/methane separation. In this study, a detailed atomistic investigation of Matrimid (R)/ZIF-8 MMM was carried out to understand the evolution of the interfacial dynamics due to plasticization when exposed to high-pressure CO2. For the analyses, a three-dimensional interface was modelled representing a ZIF-8 nanoparticle embedded in a Matrimid (R) matrix. Simulations confirmed chain rigidification of the polymer near the ZIF-8 surface. An analysis of the effect of CO2 sorption on the interface indicated that, while the interface had no significant effect on the sorption behavior up to 10 bar CO2 pressure, it emerges as the dominant sorption site at higher pressures. This study revealed two new phenomena: (1) the loading of gas molecules at the interfacial region resulted in expansion of the interface providing more space for additional CO2 sorption; and (2) the de-rigidification of previously rigidified chains in the presence of CO2. These phenomena may be the key factors in characterizing mixed gas separation performance.