This paper proposes a novel Plug-and-Play (PnP) dynamic approach for the monitoring of Large-Scale Systems (LSSs). The proposed architecture exploits a distributed Fault Detection and Isolation (FDI) methodology for nonlinear LSS in a PnP framework. The LSS consists of several interconnected subsystems and the designed FDI architecture is able to manage plugging-in of novel subsystems and un-plugging of existing ones. Moreover, the proposed PnP approach performs the unplugging of faulty subsystems in order to avoid the propagation of faults in the interconnected LSS. Analogously, once the issue has been solved, the disconnected subsystem can be re-plugged-in. The reconfiguration processes involve only local operations of neighboring subsystems, thus allowing a distributed architecture.