Dynamics and growth of many natural and man-made systems can be represented by large-scale complex networks. Entity interactions and community interconnections within complex networks increase the level of difficulty for the investigation on structural network properties such as robustness, vulnerability and resilience. In this dissertation, we develop methodologies based on mixed-integer programming techniques to solve challenging optimization problems that model cascading processes in complex networked systems. In particular, we seek to provide decision making recommendations for problems related to different types of cascading processes in networks commonly considered in a variety of applications: interdependent infrastructure networks a...