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 system. Analogously, once the issue has been eventually solved, the disconnected subsystem can be re-plugged-in. PnP design of local controllers and detectors allow these operation 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 LSS and an integrated PnP distributed FD architecture is proposed. Early simulation results show the effectiveness and potentialities of the general methodology.