A systematic methodology is presented for refinery modeling and optimization on the basis of much more detailed molecular information than is used in conventional lumped methods. The novelty of this work is that it incorporates models based on microscopic understanding into optimization to achieve macroscopic improvements. A molecular matrix based on a homologous series of hydrocarbon compounds is used to, characterize refining streams. A transformation method is developed for obtaining molecular compositions from stream bulk properties. Molecular models are then built for several processes. Molecular modeling and optimization are finally integrated into an overall refinery optimization framework. Results show that molecular information can provide much better understanding and new insights into refining operation. Consequently optimization based on molecular modeling can greatly improve total profit while making quality products that satisfy environmental regulations.