This study aims to improve the energy efficiency of an industrial site by applying the thermodynamic analysis of distillation columns together with the total site integration (TSI). Several methods have been proposed in the literatures for the thermodynamic analysis of columns. All of these efforts evaluate the energy efficiency improvement potentials limited to the distillation unit; however the column is part of a process system. Therefore bigger savings can be identified by considering the column together with the background process in TSI. Moreover some of improvement options proposed by single column analysis could appear as a disadvantage in overall process integration. In this paper, the top-down column targeting approach is used for the thermodynamic analysis and the result is evaluated applying TSI. Different steps of the analysis are presented. The process energy requirements are identified and the grand composite curve (GCC) of the total site is built. The ideal and actual temperature-enthalpy (T-H) profiles of distillation columns are generated. Based on the column targeting method, improvement options are proposed with different configuration of column over reflux ratio. In addition, feed conditions, side-reboiler in the stripping section, side-condenser in the rectifying section and heat pumping systems between intermediate stages are analyzed by applying the plus minus principle. Moreover, for the heat integration of distillation to the background process, a new representation for the ideal T-H profile of column is proposed. The results of the column targeting analysis are evaluated by calculating their effect on the TSI using the GCC of the process system. The results emphasize the importance of TSI in the integration of side exchangers and heat pump to the distillation column. The application of the proposed methodology is demonstrated through an industrial case study highlighting the different steps and the potential of this approach.