Bioethanol has been proven as an alternative clean fuel for road vehicles, with the conversion of lignocellulosic waste biomasses into ethanol through economically and environmentally viable production processes becoming increasingly important. In this study, the economic feasibility of seven process configurations for integrated molasses (1 G) and lignocelluloses (2 G) bioethanol production, in combined first- and second-generation (1G2G) facilities annexed to a typical South African sugar mill, were examined. Simulations for various first generation (1 G-only), second-generation (2 G-only) and integrated 1G2G biorefinery scenarios were developed and rigorous techno-economic and sensitivity analyses were conducted. The results determined that production of 1 G-only ethanol from C-molasses obtained a better minimum ethanol selling price (MESP) of 0.68/\$/l, compared to A-molasses (1.05 \$/l) due to the significantly higher price of A-molasses (314 \$/t) relative to C-molasses (192 \$/t). The integration of 1 G and 2 G sugars for 1G2G ethanol production showed significant economic benefits (up to 50\% improvement), compared to 2 G-only ethanol production, thereby lowering the cost of lignocelluloses conversion. The 1G2G scenario that produced the most favourable MESP of 1.23 \$/litre involved the supplementation of the whole slurry of pre-treated lignocelluloses (2 G) with A-molasses (1 G) for co-fermentation of sugars by Separate Hydrolysis and Co-fermentation (SHcF). Despite technical differences between scenarios 1G2G1, 1G2G3 and 1G2G7, no significant differences could be observed in terms of MESPs (1.25, 1.23 and 1.26 \$/l, respectively), which were the lowest value among all integrated scenarios. The main drivers of the outstanding economic performance were (1) the ability of the selected fermenting microorganism to function at sufficiently high substrate concentrations without inhibition or glucose suppression, (2) economies-of-scale benefits, (3) the high yield of sugar utilization and (4) the choice of optimum process condition for cofermentation of C5 and C6 sugars.