Oxygenated species obtained from the selective chemo-catalytic refunctionalization of lignocellulosic materials and rationally formulated mixtures thereof can be tailored to the needs of advanced internal combustion engine concepts like low temperature compression-ignition or highly boosted spark-ignition combustion. In the present contribution, we present a framework for model-based formulation of biofuel blends with tailored properties by considering the fuel's molecular composition as the fundamental design degree of freedom. To this end, optimization-based reaction pathway screening is combined with mathematical fuel property prediction by means of structural group contribution and quantitative structure-property relationship modeling in order to formulate and solve an integrated product and pathway design problem. The model-based approach is envisioned (i) to guide fundamental experimental investigations of the combustion behavior of blended biofuels toward the most favorable mixtures and (ii) to identify promising conversion pathways for further elaboration by means of reaction engineering and conceptual process design. The latter is ultimately needed to bridge the gap from the mass- and energy-based molecular level analysis presented here to a process level analysis addressing the economics of the involved conversion and separation steps. A case study is dedicated to the identification of promising blends and respective production routes, for the spark-ignition (SI) engine. The goal here is to produce a 100% bioderived fuel with tailored properties from hexoses and pentoses of lignocellulosic biomass by utilizing renewable hydrogen from carbon-free energy sources such as wind or solar to boost the energy of fuel produced for a given quantity of biomass supplied.