The π-Calculus is a modeling formalism for concurrent processes. Realized as part of the plug-in based modeling and simulation framework james ii, we propose an architecture for π-Calculus-based modeling and simulation, which supports both flexibility and efficiency. Facilitating the design of new π-Calculus-based formalisms and simulators is of particular relevance in the field of computational systems biology, for which many different π-Calculus dialects and simulators have been and still are being developed. Therefore, a flexible representation of π-Calculus models is used, which is illustrated by a mapping from the biochemical variant of the π-Calculus to the representation. Simulation engines are exchangeable and even automatically configurable according to the task at hand. Moreover, we present three different simulator implementations, working on the model representation. Efficiency denotes that our architecture supports the implementation of high-performance simulators. In order to assess efficiency, we perform experiments with these simulators and compare the results to the current cutting edge implementation in the field, the Stochastic Pi Machine.