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The replacement of fossil-based products with renewable alternatives is today a major research topic. Biofuels, such as second-generation ethanol, offer a promising way to overcome dependence on fossil fuels. However, second-generation biorefineries still face bottlenecks that hinder their economic sustainability. These include challenges in pretreatment (formation of inhibitors and high costs of chemicals) and hydrolysis (high enzyme costs and low solid content) and maximizing the utilization of biomass components. To achieve economic sustainability, biorefineries can adopt approaches such as integrating first and second generation (1G and 2G) technologies, using different production alternatives, or diversifying the product portfolio. This last alternative could include the simultaneous production of biomaterials, building blocks, and others from all fractions of the materials, favoring biorefinery profitability. Techno-economic assessment plays a crucial role in assessing the economic feasibility of these approaches and provides important information about the process. This article discusses how product diversification in cellulosic biorefineries enhances their economic sustainability, based on simulation techniques and techno-economic analysis, with a comprehensive and critical review of current possibilities and future trends. The information discussed can inform stakeholders about investing in 2G ethanol biorefineries, including strategies, associated risks, and profitability, allowing better planning of different options of future ventures. [ABSTRACT FROM AUTHOR]