We discuss an interaction-based approach to study the coevolution between socio-technical networks, individual behaviors, and contagion processes on these networks. We use epidemics in human population as an example of this phenomenon. The methods consist of developing synthetic yet realistic national-scale networks using a first principles approach. Unlike simple random graph techniques, these methods combine real world data sources with behavioral and social theories to synthesize detailed social contact (proximity) networks. Individual-based models of within-host disease progression and inter-host transmission are then used to model the contagion process. Finally, models of individual behaviors are composed with disease progression models to develop a realistic representation of the complex system in which individual behaviors and the social network adapt to the contagion. These methods are embodied within Simdemics – a general purpose modeling environment to support pandemic planning and response. Simdemics is designed specifically to be scalable to networks with 300 million agents – the underlying algorithms and methods in Simdemics are all high-performance computing oriented methods. New advances in network science, machine learning, high performance computing, data mining and behavioral modeling were necessary to develop Simdemics. Simdemics is combined with two other environments, Simfrastructure and Didactic, to form an integrated cyberenvironment. The integrated cyber-environment provides the end-user flexible and seamless Internet based access to Simdemics. Service-oriented architectures play a critical role in delivering the desired services to the end user. Simdemics, in conjunction with the integrated cyber-environment, has been used in over a dozen user defined case studies. These case studies were done to support specific policy questions that arose in the context of planning the response to pandemics (e.g., H1N1, H5N1) and human initiated bio-terrorism events. These studies played a crucial role in the continual development and improvement of the cyber-environment.