Saline aquifer geological carbon sequestration (SAGCS) is considered most attractive among other options for geological carbon sequestration (GCS) due to its huge sequestration capacity. However, in order to fully exploit its potential, efficient injection strategies need to be investigated for enhancing the storage efficiency and safety along with economic feasibility. In our previous work, we have developed a new hybrid code by integration of the multi-phase CFD simulator TOUGH2 with a genetic algorithm (GA) optimizer, designated as GA-TOUGH2. This paper presents the application of GA-TOUGH2 on two optimization problems: (a) design of an optimal water-alternating-gas (WAG) injection scheme for a vertical injector in a generic aquifer and (b) the design of an optimal injection pressure management scheme for a horizontal injector in a generic aquifer to optimize its storage efficiency. The optimization results for both applications are promising in achieving the desired objectives of enhancing the storage efficiency significantly while reducing the plume migration, brine movement and pressure impact. The results also demonstrate that the GA-TOUGH2 code holds a great promise in studying a host of other problems in CO2 sequestration such as how to optimally accelerate the capillary trapping, accelerate the dissolution of CO2 in water or brine, and immobilize the CO2 plume.