This paper deals with a novel Plug-and-Play (PnP) architecture for the control and monitoring of Large-Scale Systems (LSSs). The proposed approach integrates a distributed Model Predictive Control (MPC) strategy with a distributed Fault Detection (FD) architecture and methodology in a PnP framework. The basic concept is to use the FD scheme as an autonomous decision support system: once a fault is detected, the faulty subsystem can be unplugged to avoid the propagation of the fault in the interconnected LSS. Analogously, once the issue has been solved, the disconnected subsystem can be re-plugged-in. PnP design of local controllers and detectors allow these operations to be performed safely, i.e., without spoiling stability and constraint satisfaction for the whole LSS. The PnP distributed MPC is derived for a class of nonlinear LSSs and an integrated PnP distributed FD architecture is proposed. Simulation results in two paradigmatic examples show the effectiveness and the potential of the general methodology.