This study performs a structural optimization of anatomical thin titanium mesh (ATTM) plate and optimal designed ATTM plate fabricated using additive manufacturing (AM) to verify its stabilization under fatigue testing. Finite element (FE) analysis was used to simulate the structural bending resistance of a regular ATTM plate. The Taguchi method was employed to identify the significance of each design factor in controlling the deflection and determine an optimal combination of designed factors. The optimal designed ATTM plate with patient-matched facial contour was fabricated using AM and applied to a ZMC comminuted fracture to evaluate the resting maxillary micromotion/strain under fatigue testing. The Taguchi analysis found that the ATTM plate required a designed internal hole distance to be 0.9 mm, internal hole diameter to be 1 mm, plate thickness to be 0.8 mm, and plate height to be 10 mm. The designed plate thickness factor primarily dominated the bending resistance up to 78% importance. The averaged micromotion (displacement) and strain of the maxillary bone showed that ZMC fracture fixation using the miniplate was significantly higher than those using the AM optimal designed ATTM plate. This study concluded that the optimal designed ATTM plate with enough strength to resist the bending effect can be obtained by combining FE and Taguchi analyses. The optimal designed ATTM plate with patient-matched facial contour fabricated using AM provides superior stabilization for ZMC comminuted fractured bone segments.