With the growing environmental awareness, renewable energy sources that can replace crude oil are being in-depth studied. One of these is the bio-oil, a renewable energy source that can be obtained from biomass pyrolysis. It is characterised by the fact that its components include ketones, furans, and phenols. Among the ketones, cyclopentanone, 2-butanone, and 2,3-butanedione are the most significant, as they are useful for producing fine chemicals. The first objective of the present study is the design of a suitable separation process for the mixture composed of cyclopentanone, 2-butanone, and 2,3-butanedione, considering the presence of an azeotrope between the 2-butanone and 2,3-butanedione. For this purpose, the enhanced distillation method of pressure-swing distillation is used. To the best of our knowledge, this technique has not been applied before for this particular separation, as existing studies consider the mixture as ideal and do not take into account the presence of the azeotrope. Therefore, the separation process becomes simpler. The second objective is to optimise the aforesaid process. Given the combination of real and integer variables, the high dimensionality of the problem and the constraints on the variables, it has been decided to apply a genetic algorithm as an optimisation method. The optimised variables are the number of stages and reflux ratios of the columns, the molar flow rate of the recirculation stream and the pressure of the high-pressure column. The genetic algorithm is implemented in MATLAB ® programming language, and rigorous simulations are performed using Aspen Plus ®. The optimised variables and compositions of all streams are determined; the results of the overall heating services are 12,788 kW, and cooling services are 12,512 kW for 100 kmol/h of the crude feed. By improving the process of compound separation from pyrolysis bio-oil, the present study contributes to the use of renewable resources such as biomass instead of crude oil to produce valuable chemical compounds.