The goal of this study is to evaluate the economics and energy efficiency of different biorefinery configurations which include stillage valorization strategies for bioproducts synthesis. Specifically, a mixed-integer nonlinear programming (MINLP) model is developed to identify the optimal process network, and the impact of various parameters (e.g., bioproduct selling price, production cost, and energy requirement) on the performance of the biorefinery is investigated. Results show that the optimal strategy leading to a minimum ethanol selling price of $3.44/GGE includes gamma-valerolactone deconstruction, glucose and xylose co-fermentation, heat and power generation, and does not include stillage valorization. Economic analyses indicate that the stillage valorization becomes economically viable at bioproduct selling prices above $2.0/kg for a base unit production cost and conversion coefficient of $2.0/kg bioproduct and 0.3 kg bioproduct/kg sugars, respectively. Further studies suggest that under certain scenarios, the biorefinery does not generate sufficient energy if all stillage is utilized for bioproducts production. Therefore, the utilization of stillage has to be optimized in order to achieve an energy self-sufficient biorefinery. Finally, analyses are performed to study how improvements in combinations of parameters can lead to lower cost and higher energy efficiency.