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Security agencies have found security games to be useful models to understand how to better protect their assets. The key practical elements in this work are: (i) the attacker can simultaneously attack multiple targets, and (ii) different targets exhibit different types of dependencies based on the assets being protected (e.g., protection of critical infrastructure, network security, etc.). However, little is known about the computational complexity of these problems, especially when there exist dependencies among the targets. Moreover, previous security game models do not in general scale well. In this paper, we investigate a general security game where the utility function is defined on a collection of subsets of all targets, and provide a novel theoretical framework to show how to compactly represent such a game, efficiently compute the optimal (minimax) strategies, and characterize the complexity of this problem. We apply our theoretical framework to the network security game. We characterize settings under which we find a polynomial time algorithm for computing optimal strategies. In other settings we prove the problem is NP-hard and provide an approximation algorithm.