A crucial element of the quest of curbing carbon dioxide emissions is deemed to rely on a biobased economy, which will rely on the development of financially sustainable biorefining systems enabling a full exploitation of lignocellulosic biomass (and its macrocomponents such as cellulose, hemicellulose, and lignin) for the coproduction of biofuels and bioderived platform chemicals. In this work, a general modeling framework conceived to steer decision-making regarding the strategic design and systematic planning of advanced biorefining supply networks is presented. The design task is formulated as a mixed integer linear program which accounts for the maximization of the supply chain profit, considering multiechelon, multiperiod, multifeedstock, and multiproduct aspects as well as spatially explicit features. The applicability of the proposed model, along with the use of a bilevel decomposition approach, are demonstrated with a case study of lignocellulose-based biorefining production systems in the South-West of Hungary. Results show the effectiveness of the tool in the decision-making regarding the systematic design of advanced biorefining SC networks. An economic analysis of different design configurations (i.e., centralized and distributed scenarios) through a holistic evaluation of the entire biobased SC, integrating technology superstructure, shows that both instances generate profitable investment decisions that could be equally trusted by the decision-maker unless regional restrictions are applied.