Vapor chamber is a promising thermal solution for high-power electronics. However, achieving its full potential requires well-designed sintered powder pillars, including pillar diameter, porosity, and pitch. Neglecting these pillar design factors can adversely affect thermal-hydraulic performance, leading to further failures. This paper utilizes numerical simulation and analysis of variance to visualize and analyze the phase change flow behaviors of the pillar-reinforced vapor chamber, then examines the influence of each pillar design factor on thermal resistance, temperature uniformity, and total pressure drop. The results show that, for thermal resistance, pillar porosity has the highest contribution (51.6%), while pillar pitch is moderate (13.6%), and pillar diameter only contributes 0.3%. Nonetheless, pillar diameter has the highest contribution on temperature uniformity (72.1%) and total pressure drops (49.0%). Besides, the results also suggest that when the pillar diameter is larger than a certain value, the thermal resistance and total pressure drop can increase due to excessive vapor flow resistance and limited liquid circulation to the heat source. The optimization results suggest that the desirability of 0.77 balances all responses for the best overall thermal-hydraulic performance. The results inform that the trend of each response is generally aligned for some factors and opposite for others.