Effects-Based Operations (EBO) refers to a process for achieving strategic goals by focusing on effects rather than attrition-based destruction. For a successful implementation of EBO, identifying key nodes in an adversary network is crucial in the process of EBO. In this study, we suggest a network-based approach that combines network centrality and optimization to select the most influential nodes. First, we analyze the adversary’s network structure to identify the node influence using degree and betweenness centrality. Degree centrality refers to the extent of direct links of a node to other nodes, and betweenness centrality refers to the extent to which a node lies between the paths connecting other nodes of a network together. Based on the centrality results, we then suggest an optimization model in which we minimize the sum of the main effects of the adversary by identifying the most influential nodes under the dynamic nature of the adversary network structure. Our results show that key node identification based on our optimization model outperforms simple centrality-based node identification in terms of decreasing the entire network value. We expect that these results can provide insight not only to military field for selecting key targets, but also to other multidisciplinary areas in identifying key nodes when they are interacting to each other in a network.