Abstract The subject of energy saving in distillation column sequencing is of critical importance. Heat integration in a multicomponent separation can be industrialized by saving considerable energy and cost. In this work, external heat-integrated distillation column with external heat exchanger has been studied and the annual cost function has been optimized using Genetic Algorithm. Introducing the layout and binary matrices enabled the investigation of all possible locations for the heat exchanger arrangement successfully. Moreover, exchangers heat loads and compressors pressure, have also been considered as optimization variables. Benzene, toluene, xylene and n-alkanes, separations have been studied as case studies. It has been demonstrated that the proposed optimization method in the alkane separation case decreased the total annual cost by 22.6% in comparison with the proposed thermally coupled distillation sequence columns. The heat integration of external heat exchangers in an external heat-integrated distillation column configuration and the proposed dived-wall column resulted in decreasing the total annual cost by 17% and 39% respectively, in comparison with conventional distillation columns.