Growing demand for energy worldwide has increased interest in the production of renewable fuels, with microalgae representing a promising third generation feedstock. This study presents the use of a modular engineering process model, informed through literature, to evaluate the nitrogen and phosphorus resource demand of five microalgae to biofuels production systems. The baseline scenario, representative of an economically viable large-scale production system, includes sub-process models for growth, dewater, lipid extraction, anaerobic digestion, and biofuel conversion. Baseline modeling results combined with current US resource availability from fertilizer and wastewater show nitrogen and phosphorus requirements represent a potential barrier to the large-scale development of microalgae based biofuels. Baseline results show municipal wastewater sources can provide sufficient nutrients to produce 3.8 billion gallons of fuel per year, corresponding to 6% of the DOE goal of 60 billion gallons per year. Results from modeling of alternative production scenarios shows hydrothermal liquefaction to be a promising technology in terms of resource consumption. The use of lipid extracted algae as a value-added coproduct is shown to be limitting due to nutrient recovery requirements for scalability. Optimistic and conservative process scenarios are simulated to bound the total resource demand and represent practical best and worst case scenarios. (C) 2016 Elsevier Ltd. All rights reserved.