The integrated biorefinery has the opportunity to provide a strong, self-dependent, sustainable alternative for the production of bulk and fine chemicals from polymers, fiber composites and pharmaceuticals to energy, liquid fuels and hydrogen. With such a wide range of processing steps and possible products, it is obvious that identification of the optimum process structure can not be done based on heuristics or rules of thumb. Thus, there is a need for systematic, reliable methods capable of incorporating different levels of process detail in the decision making framework. By constructing simulation models for various biorefining processes, determining variable and fixed cost components of these processes, and combining this cost data with information on expected return and market conditions, firms interested in biorefining will be able to determine the effects of changes in value as a result of deciding which products to pursue among the many biorefinery possibilities. Through quantifying the level of environmental impact using EPA's WAR algorithm, sustainability could then be measured on a relative scale. An inherent benefit of the proposed framework comes from the decoupling of the complex models from the selection step, which results in the ability to adapt to new developments within any of the processing steps and thus also incorporate novel innovative production processes in the decision-making framework. In this way, experimental and theoretical efforts can supplement each other in a synergistic manner, by providing direction and data for continued work. Changing market conditions may dictate a dynamic optimum for the allocation of resources and production capacity, resulting in a myriad of possible long-term product portfolios and a need for a net present value perspective that takes into account the time value of money. This contribution will illustrate the strategy for developing the decision making framework as well as highlighting the flexibility of the framework to utilize data from technological breakthroughs in the field of biorefining.