The transition from fossil to renewable resources requires energy-efficient technologies and approaches in chemicals production. Critical aspects for energy and resource consumption are distillation columns due to their high energy demand and low energy efficiency. Therefore, the optimal design of distillation columns is crucial for increasing the overall energy efficiency. In this contribution, we present the application of the FluxMax approach to the separation section of the methanol synthesis. The FluxMax approach enables the simultaneous flux optimization and heat integration of chemical processes by discretization of the thermodynamic state space. As a consequence, the process-based nonlinearities are effectively decoupled from the subsequent flow optimization problem. The distillation process is represented by the elementary processes mixing, heating, cooling, and flash separation. By simultaneously considering heat integration in the optimization problem, each tray of the distillation column can be represented by means of the introduced elementary processes. The optimal number of trays and the optimal reflux ratio are direct results of the flux optimization. The FluxMax approach is applied to the methanol–water separation using two different objective functions: energy minimization and tray number minimization. The presented results provide the proof of concept for the use of the FluxMax approach to the synthesis of distillation columns that can be embedded in an overall process optimization.