Previous studies have investigated the overall performance of the modified Solvay process based on a new alkaline compound, namely, KOH. Preliminary results have confirmed its high reactivity and effectiveness in capturing CO2 and managing reject brine. In this study, parametric sensitivity analysis has been carried out to optimize the operating conditions and thereby maximize CO2 capture and ions removal from high-salinity brines. Response surface methodology (RSM) analysis using the central composite design (CCD) approach was implemented to statistically determine the impact of important operating conditions, including KOH concentration (30–110 g/l), CO2 gas flow rate (400–1600 ml/min), gauge pressure (1–3 barg), and temperature (10–50 °C) on key response process output variables, such as CO2 uptake and ions reduction. The importance of these parameters and their interactions were confirmed by employing analysis of variance (ANOVA) approach at a confidence level of 95% (p < 0.05). These analyses demonstrated that under the optimized conditions of a temperature of 10 °C, gauge pressure of 2.1 barg, CO2 gas flow rate of 848.5 ml/min, KOH concentration of 110 g/l, and an inert mixing particle volume fraction of 15%, a maximum CO2 uptake value of 0.58 g/g KOH, maximum sodium removal of 44.1%, chloride ( removal of 40.1%, calcium ( removal of 100%, and magnesium ( removal of 99.8% were achieved. The characterization of the collected solid products at optimum conditions revealed the production of valuable and useful products, particularly sodium and potassium bicarbonates, in addition to KCl.