Micromotion magnitudes exceeding 150 µm may prevent bone formation and limit fixation after cementless total knee arthroplasty (TKA). Many factors influence the tray–bone interface micromotion but the critical parameters and sensitivities are less clear. In this study, we assessed the impacts of surgical (tray alignment, tibial coverage, and resection surface preparation), patient (bone properties and tibiofemoral kinematics), and implant design (tray feature and surface friction) factors on tray–bone interface micromotions during a series of activities of daily living. Micromotion was estimated via three previously validated implant-bone finite element models and tested under gait, deep knee bending, and stair descent loads. Overall, the average micromotion across the tray–bone cementless contact interface ranged from 9.3 to 111.4 µm, and peak micromotion was consistently found along the anterior tray edge. Maximizing tibial coverage above a properly sized tibial tray (an average of 12.3% additional area) had minimal impact on micromotion. A 1 mm anterior tray alignment change reduced the average micromotion by an average of 16.1%. Two-degree tibial angular resection errors reduced the area for bone ingrowth up to 48.1%. Differences on average micromotion from ±25% changes in bone moduli were up to 75.5%. A more posterior tibiofemoral contact due to additional 100 N posterior force resulted in an average of 79.3% increase on average micromotion. Overall, careful surgical technique, patient selection, and controlling kinematics through articular design all contribute meaningfully to minimizing micromotion in cementless TKA, with centralizing the load transfer to minimize the resulting moment at the anterior tray perimeter a consistent theme.