Sesquiterpenes are a group of versatile, 15‐carbon molecules with applications ranging from fuels to fine chemicals and pharmaceuticals. When produced by microbial fermentation at laboratory scale, solvents are often employed for reducing product evaporation and enhancing recovery. However, it is not clear whether this approach constitutes a favorable techno‐economic alternative at production scale. In this study empirical correlations, mass transfer and process flow sheeting models were used to perform a techno‐economic assessment of solvent‐based processes at scales typical for flavors and fragrances (25 MT year−1) and the fuel market (25 000 MT year−1). Different solvent‐based process options were compared to the current state of the art, which employs surfactants for product recovery. The use of solvents did reduce the sesquiterpene evaporation rate during fermentation and improved product recovery but it resulted in costs that were higher than, or similar to, the base case due to the additional equipment cost for solvent‐product separation. However, when selecting solvents compatible with the final product formulation (e.g. in a kerosene enrichment process), unit costs as low as $0.7 kg−1 can be achieved while decreasing environmental impact. © 2018 The Authors. Biofuels, Bioproducts and Biorefining published by Society of Chemical Industry and John Wiley & Sons, Ltd.