Due to the high costs of 3D-printing infrastructure, outsourcing the production to third parties specializing in the 3D-printing process becomes necessary. The integration of a 3D-printing system with networked communications constitutes a cyber-physical system, bringing new security challenges. Adversaries can explore the vulnerabilities of networks to damage the physical parts of the system. In this chapter, we explore the vulnerabilities of 3D-printing systems and design a cross-layer approach for the system. At the physical layer, we use a Markov jump system to model the system and develop a robust control policy to deal with uncertainties. At the cyber-layer, we apply FlipIt game to model the contention between the defender and attacker for the control of the 3D-printing system. To connect these two layers, we develop a Stackelberg framework to capture the interactions between the cyber-layer attacker and defender game and the physical-layer controller and disturbance game, and define a new equilibrium concept that captures interdependence of the zero-sum and FlipIt games.