The expanse of U.S. transportation systems has helped to facilitate persistent national economic growth, its ease of access and reliability vital to the plethora of users who utilize daily the established infrastructure. Recent events have shown cause for concern, however, as the vulnerability inherent in such transportation systems has been exploited by the calculated attacks of highly motivated individuals and groups who have used these networks to target the connected critical infrastructure and human populations. This research focuses on the protection of large geographic regions, and the critical components contained within, in their susceptibility to covert attacks using hazardous materials vehicles as the tool of implementation. Focusing on the detection and interception of such attacks, this work introduces three mathematical models responsible for the placement of varying types of sensors within a geographic region of interest and employs a hypercube spatial queuing model to ascertain response unit functionality and capability given the sensor network schema. The regions of Lancaster-Palmdale, California and Northridge, California are used in the systematic examination of model performance and solution characteristics. A case study within the region of Los Angeles County, California is offered as a demonstration of the success of the model to cope with networks and parameters of realistic scope and scale. The results of model implementation show trends in the application of sensor networks as a means to regional vulnerability reduction and infrastructure protection and illustrate the relationship between sensor placement and the successful instantiation of a response team and the allocation of its individual units. The complete model relies heavily on a Geographic Information System (GIS) for the manipulation and management of all network and sensor data and combines integer programming and queuing theory concepts in the development of an integrated detection and interception model for the protection of multiple points of critical infrastructure within a large geographic region.