A comprehensive thermo-economic model combining a geothermal heat mining system and a direct supercritical CO₂ turbine expansion electric power generation system was proposed in this paper. Assisted by this integrated model, thermo-economic and optimization analyses for the key design parameters of the whole system including the geothermal well pattern and operational conditions were performed to obtain a minimal levelized cost of electricity (LCOE). Specifically, in geothermal heat extraction simulation, an integrated wellbore-reservoir system model (T2Well/ECO2N) was used to generate a database for creating a fast, predictive, and compatible geothermal heat mining model by employing a response surface methodology. A parametric study was conducted to demonstrate the impact of turbine discharge pressure, injection and production well distance, CO₂ injection flowrate, CO₂ injection temperature, and monitored production well bottom pressure on LCOE, system thermal efficiency, and capital cost. It was found that for a 100 MW_e power plant, a minimal LCOE of $0.177/kWh was achieved for a 20-year steady operation without considering CO₂ sequestration credit. In addition, when CO₂ sequestration credit is $1.00/t, an LCOE breakeven point compared to a conventional geothermal power plant is achieved and a breakpoint for generating electric power generation at no cost was achieved for a sequestration credit of $2.05/t.