Since the vast majority of carbon dioxide (CO₂) storage resources in the United States are in deep saline aquifers, optimizing the use of these saline storage resources could be crucial for efficient development of geologic CO₂ storage (GCS) resources and basin- or larger-scale deployment of GCS in the country. Maximum CO₂ injection rates can be enhanced by extracting brine from the CO₂ storage unit. However, disposal of the extracted brine is both a technological and economic challenge. The lowest-cost option would likely be reinjection of the extracted brine into another formation above or below the CO₂ storage unit. Therefore, it is important to estimate brine injectivity as it will constrain the potential to increase CO₂ injectivity at an injection site that has access to multiple geologic storage units where either CO₂ or brine can be injected. Using a simulation-optimization framework, coupled with a non-isothermal, multiphase CO₂-water-salt equation-of-state module, we developed a computationally efficient method for evaluating optimization of simultaneous CO₂ injection, brine extraction, and brine (re)injection at hypothetical injection sites deployed across a geologic basin. The Illinois basin is ideal for testing our methodology because it contains multiple geologic storage units with seals in between them to isolate injection of CO₂ in one unit from interfering with the injection of either brine or CO₂ in another unit above or below it. In addition, we investigated the relative effects of variation in key geologic parameters as well as two reservoir structures (hydrogeologic heterogeneity/anisotropy and homogeneity/isotropy) on CO₂ injectivities and enhancement of CO₂ injectivity through extracting brine. Results suggest that permeability, depth, and especially thickness of the storage unit could be the most influential parameters determining CO₂ injectivity. They also suggest that only injecting CO₂ into the storage unit with the greatest injectivity, enhancing that unit’s injectivity by extracting brine, and disposing of the produced brine in other suitable units could maximize total CO₂ injectivity in limited regions of the basin. At the majority of simulated injection sites, however, we found that injecting CO₂ into all of the accessible and suitable storage units was more likely to maximize the CO₂ storage resource.