Renewable energy plays a key role in the fight to reduce greenhouse gas emissions while providing for human well-being and economic development. However, despite environmental benefits in terms of carbon sequestration, largely promoted biorenewable resources such as sugarcane and corn starch, so-called 1st generation (1G) feedstocks, are associated with other types of social and environmental issues that highly contradict the notion of sustainability, such as the food versus fuel conflict and the contribution to impacts such as deforestation, soil degradation, loss of biodiversity and contamination of water resources. As reaction to these issues, a lot of effort has been put into the development of technologies to extract and convert useful energy from non-food crops and agro-industrial residues, such as sugarcane bagasse, corn stover, and wheat straw. These now called 2nd generation (2G) feedstocks offer an extra challenge since fermentable sugars are not readily available; nonetheless, myriad technologies have been (and are being) developed to convert 2G materials into fuels and chemicals, with perhaps the most representative product being ethanol, a widely employed engine fuel and gasoline additive. 2G or cellulosic ethanol can be produced via biochemical pathways, thermochemical pathways, or a third option that combines aspects of the other two, commonly called the thermo-biochemical, or hybrid, pathway. The latter is the focus of this thesis, which explores this pathway via process modeling, simulations, (multi-objective) optimization, and other strategies applied in order to determine which process choices and conditions lead to the best performance in terms of main sustainability aspects. While the thermochemical process of gasification enables the nearly full conversion of biomass without the need for complex and expensive stages of pretreatment and hydrolysis, the subsequent biological conversion (fermentation) of syngas might offer several advantages when compared to the traditional catalytic conversion, e.g. higher flexibility of H2:CO ratios and tolerance to gas contaminants . Although certain challenges may drawback the commercial competitiveness of syngas fermentation, such as the low productivity when compared to heterotrophic fermentation, intelligent choices of process integration and design parameters could substantially enhance the performance of the process.