Systems and methods for Internet-of-Things (IoT) gateway tampering detection and management. In some embodiments, an Information Handling System (IHS) may include a processor and a memory coupled to the processor, the memory including program instructions stored thereon that, upon execution by the processor, cause the IHS to: identify a priority value for each of a plurality of IoT devices coupled to the IHS, detect an event indicative of physical tampering of the IHS, and initiate an action in response to the detection, wherein the action is based, at least, in part, upon the priority values.