The objective of this review is a global assessment of the economics of second‐generation biorefineries, with a focus on the use of food waste and agricultural residues for chemical production by applying biotechnological processes. Analyses are conducted on feedstock and product distribution, applied economic models, and profitability figures for the period 2013–2018. In a study of 163 articles on different biorefinery systems, the production of chemicals is identified as the second major product class, after bioenergy. Bagasse and straw are frequently analyzed second‐generation feedstocks. Based on the evaluation of 22 articles, second‐generation biorefineries producing chemicals by applying biotechnological processes proves to be economically feasible. On average, both the internal rate of return (IRR) and the return on investment (ROI) are 20% and the payback period (PP) is 6 years. The cost share of feedstock in biorefineries is between 0–50%. The price of the end product and the fermentation yields have the most impact on profitability. The processing of food waste that has industrial and municipal origins appears more economical than the processing of agricultural residues. Scientists, policy makers and entrepreneurs with an appropriate risk tolerance are advised to pay particular attention to municipal food waste and the potential economic production of carboxylic acids. For various economic issues related to biorefineries, dynamic‐deterministic models are recommended, which can be extended by a stochastic model. This review provides an initial overview of the economic feasibility of second‐generation biorefineries. Further techno‐economic analyses are required to produce statistically significant statements on key profitability figures. © 2020 The Authors. Biofuels, Bioproducts, and Biorefining published by Society of Chemical Industry and John Wiley & Sons, Ltd.