Fused deposition modeling (FDM) processed Poly-ether-ether-ketone (PEEK) materials are widely used in aerospace, automobile, biomedical, and electronics industries and other industries due to their excellent mechanical properties, thermal properties, chemical resistance, wear resistance, and biocompatibility, etc. However, the manufacture of PEEK materials and parts utilizing the FDM process faces the challenge of fine-tuning a list of process parameters and heat treatment conditions to reach the best-suiting mechanical properties and microstructures. It is non-trivial to make the selection only according to theoretical analysis while counting on a vast number of experiments is the general situation. Therefore, in this paper, the extrusion rate, filling angle, and printing orientation are investigated to adjust the mechanical properties of 3D-printed PEEK parts; then, a variety of heat treatment conditions were applied to tune the crystallinity and strength. The results show that the best mechanical performance is achieved at 1.0 times the extrusion rate, varied angle cross-fillings with ±10° intervals, and vertical printing. Horizontal printing performs better with reduced warpage. Additionally, both crystallinity and mechanical properties are significantly improved after heat treatment, and the best state is achieved after holding at 300 °C for 2 h. The resulting tensile strength is close to 80% of the strength of injection-molded PEEK parts.