Clinical findings, manufacturer instructions, and surgeon’s preferences often dictate the implantation of distal femur locked plates (DFLPs), but healing problems and implant failures still persist. Also, most biomechanical researchers compare a particular DFLP configuration to implants like plates and nails. However, this begs the question: Is this specific DFLP configuration biomechanically optimal to encourage early callus formation, reduce bone and implant failure, and minimize bone “stress shielding”? Consequently, it is crucial to optimize, or characterize, the biomechanical performance (stiffness, strength, fracture micro-motion, bone stress, plate stress) of DFLPs influenced by plate variables (geometry, position, material) and screw variables (distribution, size, number, angle, material). Thus, this article reviews 20 years of biomechanical design optimization studies on DFLPs. As such, Google Scholar and PubMed websites were searched for articles in English published since 2000 using the terms “distal femur plates” or “supracondylar femur plates” plus “biomechanics/biomechanical” and “locked/locking,” followed by searching article reference lists. Key numerical outcomes and common trends were identified, such as: (a) plate cross-sectional area moment of inertia can be enlarged to lower plate stress at the fracture; (b) plate material has a larger influence on plate stress than plate thickness, buttress screws, and inserts for empty plate holes; (c) screw distribution has a major influence on fracture micro-motion, etc. Recommendations for future work and clinical implications are then provided, such as: (a) simultaneously optimizing fracture micro-motion for early healing, reducing bone and implant stresses to prevent re-injury, lowering “stress shielding” to avoid bone resorption, and ensuring adequate fatigue life; (b) examining alternate non-metallic materials for plates and screws; (c) assessing the influence of condylar screw number, distribution, and angulation, etc. This information can benefit biomedical engineers in designing or evaluating DFLPs, as well as orthopedic surgeons in choosing the best DFLPs for their patients.