The furanic chemical 2,5-dimethylfuran (DMF) is an attractive biobased fuel and feedstock. High-yield biphasic processes for DMF synthesis from sugars employ higher alcohols such as n-butanol (BuOH) as solvents. This leads to a product containing <8 wt % DMF and byproducts in the BuOH solvent along with water. DMF process economics are dominated by separation costs for DMF purification and recycle of BuOH and water. We previously demonstrated efficient adsorptive separation of DMF with a stable ZIF-8 metal–organic framework adsorbent. Here, we present a detailed, comparative technoeconomic analysis and sustainability indicators of adsorptive versus conventional distillation separation processes to produce 98 wt % pure DMF at 100 metric tons/day. The novel adsorptive process integrates a simulated moving bed (SMB) unit with water removal and desorbent recovery systems, whereas the distillation process relies on multiple columns operating at different pressures to handle the strongly nonideal multicomponent thermodynamics. Rigorous process modeling is conducted by a combination of the Aspen Plus flowsheet simulation package and our in-house SMB modeling and optimization package, with realistic multicomponent adsorption and vapor–liquid equilibrium models parametrized by experimental data. This is followed by detailed calculations and sensitivity analysis of bare-module, utility, and material costs. The net present values (NPVs) of the process alternatives show a clear long-term economic advantage of the adsorptive process, mainly due to large reduction in utility costs. For a 100 MTD DMF plant, the ΔNPV for adsorptive separation is strongly positive (>$6M at a 10% discount rate and 15-year operation) and remains competitive over a large range of sensitivity factors. When translated to a large potential DMF biofuel market size similar to that of bioethanol, the SMB-based adsorptive process would save >$8B/yr. globally in separation costs. Furthermore, the novel adsorptive process has much better sustainability indicators, including 41% lower process energy intensity and 37% lower process CO2 emissions, as well as a number of qualitatively determined environmental and safety advantages.