The thermal performance of cold chain containers is very important to guarantee the quality of food and medicine in short-term transportation. Semiconductor chill/warm portable containers are applied in the cold chain industry, and Vacuum insulation panels (VIPs) are employed as thermal insulation materials. A cold chain portable container integrating with semiconductor and vacuum insulation panel (VIP) enclosures was reported in this paper. Two different locations of semiconductors were designed and simulated. The result revealed that, the temperature distribution was uniform to avoid deterioration caused by the accumulation of the good while the semiconductor was placed at the top section. VIP and polyurethane (PU) were involved to form multi-layer insulation systems (MLIS) in container enclosures. Three models were developed according to the VIP layout, that is, external, sandwich, and internal insulation. Chill /warm container experiments were carried out to prove that the external insulation container took the best thermal insulation behavior. When integrated with a semiconductor located at the top, it shows the longest duration time accompanied by lower temperature. The thermal performances of MLIS were compared to explore the possibility of potential for small cold chain device applications.