The objective of our study was to quantify the biomechanical effectiveness of lateralization in RTSA with respect to glenoid and humeral component configurations. Eight cadaveric shoulders were tested in a custom shoulder testing system. Three parameters, including the glenosphere thickness, humeral tray offset and insert thickness, were assessed by implanting eight configurations on each specimen. Humeral position, maximum internal rotation, and maximum external rotation (ER) before impingement were quantified at 0°- and 30°- glenohumeral abduction. The adduction angle at which the humeral component contacted the inferior scapular neck and the abduction angle where acromial notching occurred were also measured. The simulated active range of motion, including ER and abduction capability, was tested by increasing the load applied to the remaining posterior cuff and middle deltoid, respectively. Stability was evaluated by the forces that induced anterior dislocation at 30° abduction. The thicker glenosphere affected only lateralization, whereas the centric humeral tray and thicker insert significantly affected humeral lateralization and distalization simultaneously. Greater adduction and ER angles were found in more lateralized humerus. A significant positive correlation between humeral lateralization and ER capability was observed; however, lateralization did not significantly improve implant stability in this cadaveric testing system. Lateralization is achievable at both the glenoid and humeral sides but has different effects, therefore lateralized implant options should be selected according to patients' needs. Lateralization is an effective strategy for reducing adduction notching while increasing ER capability. Thicker glenospheres only affected humeral lateralization. The centric humeral tray would be selected for less distalization to avoid over-lengthening, whereas an eccentric humeral tray is the most effective for distalization and medialization in reducing abduction notching to the acromion and for patients with pseudoparalysis.