First generation ethanol (1G) contributes to the majority of the ethanol produced worldwide, predominantly centered on corn and sugarcane. Nevertheless, several issues are regularly highlighted concerning the long-term sustainability of this technology, including its intensive water and land use, potential contamination of soils through the distillation residues, as well as the balance between fuel and food crops. Accordingly, in this study, a process design approach for biomass to ethanol production (1G ethanol technology) from sugarcane was performed by using Aspen Plus (R) software, based on the autonomous distillery (AUT, ethanol production) and the annexed plant (ANX, joint ethanol and sugar production) configurations. In addition, a performance comparison in respect to the exergy efficiency and the irreversibility as quality indicators of the conversion processes is carried out to identify potential improvements in the production facilities. Hence, the shortcomings of the techno-economic assessment of ethanol production can be overcome by using exergy efficiency as a suitable indicator for process performance. Moreover, the technical/sustainability aspects related to the process design of the sugarcane biorefineries are discussed in light of the renewability exergy index (lambda). In general, the ANX plant has a saving in the process irreversibility rate of about 6 %, whereas the average unitary exergy cost is 10% lower (AUEC= 2.41 kJ/kJ), in contrast to the AUT distillery. Moreover, a techno-economic analysis was carried out to assess the annexed plant and the autonomous distillery systems, considering the estimated capital expenditure. The results indicated that the ANX biorefinery has higher capex than the AUT distillery. It is noted that the higher investments are associated with sugarcane reception, ethanol production (juice extraction) and the combined heat and power sub-systems. Concerning system performance, the ANX plant presented a better overall exergy efficiency, with 41.39 %. Although this multi-criteria analysis is applied to 1G ethanol technology; it may be well-matched for various biorefineries/bioprocesses as a methodology to support decision-making as concerns potential improvement, well ahead of detailed process design.