Differing from managing a general supply chain, handling environmentally sensitive products (ESPs) requires the use of specific refrigeration systems to control the designated range of storage conditions, such as temperature, humidity, and lighting level in a cold chain environment. In general, third-party logistics (3PL) companies are authorized to handle ESPs, who therefore need to have a good cargo monitoring system in the cold chain environment, without which the functional quality is difficult to control and manage. This may result in product deterioration and even inventory obsolescence of the ESPs due to the lack of such systems, so there is a need to develop an effective cargo monitoring system to prevent such situations. This article proposes an Internet of Things-based cargo monitoring system (IoT-CMS) to monitor any environmental changes of ESPs in order to ensure their functional quality throughout the entire cold chain operational environment. Operational efficiency, maintenance strategy, environmental change, and electricity consumption are considered in real-life cold chain operations. Through applying (i) a wireless sensor network to collect real-time product information, together with (ii) fuzzy logic and case-based reasoning techniques to suggest appropriate storage conditions for various ESPs, effective storage guidance can be established. Through conducting the case study in a 3PL company in Hong Kong, the performance in customer satisfaction, obsolescence rate, and inventory visibility after adoption of IoT-CMS is evaluated. It is found that the functional quality of ESPs can be effectively assured, and the overall customer satisfaction is increased.