Driven by the increasing demand for high-power systems, ceramic substrates have received more attention for handling higher power density. Warpage in active metal brazed (AMB) ceramic substrate becomes a critical issue as it can deteriorate the reliability performance. This study comprises three phases, including investigation of the cause of the warpage, validation of the proposed model, and optimization for effective warpage management. At first, the coefficient of thermal expansion (CTE) and yield strength of the copper (Cu) layer in AMB were characterized and adopted in a two-dimensional (2D) finite element model. The evolution of simulated strain and moments revealed the cause of the warpage during the manufacturing processes. Furthermore, the 2D model was extended to a three-dimensional (3D) model. The finite element method (FEM) and experiments were conducted on different heat treatment conditions for 3D model validation. The validated 3D model was applied to carry out a design of experiments (DoEs) for design optimization to reduce the warpage. Consequently, the factor analysis in DoEs was demonstrated by different pattern designs using subtractive milling techniques.