Even though a shift from conventional to renewable resources is often envisaged, lignocellulosic biorefinery concepts struggle with economic viability and sustainability. In order to overcome these barriers, a full analysis from biomass supply chain, process performance optimization, and product-portfolio selection is targeted. Addressing the economic viability and sustainability already at an early process development stage when only limited knowledge is available, Process Network Flux Analysis (PNFA) [Ulonska et al., AIChE J. 2017, 62, 3096-3108] is capable of systematically identifying the most valuable processing pathways. This enables a first performance ranking based on the profit or global warming potential of pathways, thereby accelerating process development. While so far only processing networks have been considered, the methodology is herein extended to consider biomass supply chain optimization and market-dependent price developments such that all main influencing factors are considered simultaneously. The extended methodology is validated identifying reasonable plant locations in North Rhine-Westphalia, Germany. Enhancing economic viability of the best performing biofuel ethanol, a multiproduct biorefinery is targeted coproducing value-added chemicals. Herein, a coproduction of iso-butanol raises the profit significantly: a mass ratio of at most 1.9 (ethanol:iso-butanol) is required to break even.