Diesel emission regulations for cars and trucks are becoming ever more stringent, and it is important to be able to evaluate the performance of new after-treatment technologies and architectures and their effects on the powertrain and vehicle. This paper presents a new modeling and simulation methodology that treats the entire exhaust system, not just one component. In order to achieve this, a modeling architecture is developed based on a statevector platform where component sub-models can be easily developed and integrated, forming a larger system which can simulate vehicle operations. The innovation presented in this paper is the modular simulation architecture that allows investigation of a large number of different system architectures without having to manually parameterize each configuration. The system model can then be used as the basis from which multidisciplinary, multi-objective, system-wide analysis can be performed. The framework is applied to the optimization of a commercial vehicle diesel exhaust treatment system, including a diesel oxidation catalyst and other components.