This work presents a two-step method to reduce the energy consumption (in terms of the reboiler duty) of a natural gas sweetening process via a physical-chemical solvent mixture (Step 1) followed by a techno-economic analysis of 15 different absorber-stripper configurations (Step 2). Initially, an amine-based sweetening process using a H2S-free sour gas was simulated on Aspen HYSYS and the simulation results were validated against real plant data. In Step 1, different ratios of Sulfinol-M and Sulfinol-D based sweetening process were simulated and the superior physical-chemical solvent mixture that provides the lowest reboiler duty while meeting the sweet gas CO2 product concentration specification (i.e., less than 2 mol.%) is the Sulfinol-M solvent that contains 38 wt.% methyl diethanolamine (MDEA), 40 wt.% Sulfolane, and 22 wt.% water. This Sulfinol-M based model is then optimized via a parametric analysis to further improve its performance in terms of the reboiler duty prior to Step 2. The optimized Sulfinol-M based model achieved 65% saving in the reboiler duty while fulfilling the CO2 concentration specification in product gas relative to the base case. In Step 2, four main absorber-stripper configurations, namely absorber intercooling (AI), lean amine stream split flow (LASSF), rich amine stream split flow (RASSF), and mechanical vapor recompression (MVR) along with their 11 possible combinations were simulated in an attempt to decrease the energy consumption of the process and hence, ranked based on their total cost of production (TCOP). The results revealed that the integration of LASSF + RASSF provides the best option as it achieved the lowest TCOP of $4.60 M while fulfilling the CO2 concentration in product gas and contributed to 6.39% savings in the reboiler duty compared to the optimized conventional Sulfinol-M based model.