This paper proposes several novel multi-effect dividing wall column (MEDWC) configurations to retrofit and debottleneck side-stream columns or two-column sequences for multiple objectives such as increasing the column throughput, maximizing energy efficiency, and reducing carbon dioxide (CO2) emissions. This paper also proposes a new practical method that employs a coordinate descent methodology, which is assisted by a random search to avoid local optimal points and box search to overlook more promising solutions for optimal retrofitting. One industrial case was studied and analyzed to demonstrate the proposed configuration. The results show that the proposed modified coordinate descent methodology not only effectively avoided the local optimal points but also overlooked more promising solutions. The proposed method is competitive with the coordinate descent methodology and response surface methodology, which are popular optimization methods used in the chemical process industry. Both the structural and operating variables are effectively and simultaneously optimized. The proposed MEDWC sequence removes the bottleneck problem effectively and achieves substantial energy savings and CO2 emissions reduction. Notably, a 73.2% and 73.6% reduction in operating costs and CO2 emissions, respectively, can be achieved in the ethylene dichloride separation processes. The proposed configuration can be applied to both close-boiling and wide-boiling mixtures.