The heat-integrated air separation column (HIASC) is a highly energy-efficient air separation technology, but its application in industries has been limited due to its complexity and high equipment costs. In this paper, three different HIASC configurations, namely, full internal thermally coupled (F-HIASC), partial internal thermally coupled (P-HIASC), and external thermally coupled (E-HIASC), are designed and optimized to mitigate this complexity. This design correlates F-HIASC and energysaving alternative schemes through P-HIASC and E-HIASC, respectively. These configurations are then optimized to minimize energy consumption and heat exchanger costs. An optimization process was executed by incorporating the HIASC model into a reduced sequential quadratic programming (rSQP) algorithm. A ternary system of nitrogen, oxygen, and argon was chosen to assess the performance of HIASC configurations on the basis of energy saving and operating costs, and it was benchmarked against a heatintegrated air separation unit (HI-ASU). The energy-saving performance in the P-HIASC is significantly improved compared to that in the other HIASC configurations. Also, the E-HIASC and P-HIASC outperform the HI-ASU by 26.97% and 29.53% reduction in total annual cost (TAC), respectively. Contrary to the lower difference in TAC reduction between P-HIASC and E-HIASC, the latter is fairly simple to build. The structural optimization of the HIASC results in improved energy efficiency, cost reduction, and operation stability.