Three-dimensional (3D) mesh fabric is a key component in ventilated car seats for its excellent cushioning and ventilating performance. It is produced by stretching an as-knitted spacer fabric with closed surfaces via stentering and fixing the mesh form via heat-setting. This paper analyzes the effect of stentering and heat-setting processes on the structures and compression properties of a typical and commercial 3D mesh fabric by using X-ray micro-computed tomography (μCT) and finite element (FE) models. The monofilament architectures of the fabric after knitting, stentering, and heat-setting are reconstructed from μCT scanning, and the structural evolution is quantitatively investigated in terms of global dimension change, curvature, and torsion. The results from μCT reconstructions demonstrate that stentering shortens, widens, and thins the fabric due to yarn transfer to shorten monofilament loops and lengthen spacer monofilaments, which are then dispersed, bent, and twisted to increase the curvatures and torsions. The FE simulations indicate that the global and local monofilament architecture deformation shifts the fabric compression mode from constrained post-buckling to concurrent tilting and post-buckling of spacer monofilaments, expanding the plateau stage and decreasing plateau stress. Heat-setting shrinks monofilament and therefore deteriorates its mechanical performance. The fabric is further thinned during the heat-setting process, which also further bends and twists spacer monofilaments to slightly decrease the plateau stress. The structures and cushioning performance of 3D mesh fabrics can be engineered by employing a proper stentering ratio followed by a heat-setting process.