Implant malalignment has been reported to be a primary reason for revision total knee arthroplasty (TKA). In addition, altered muscle coordination patterns are commonly observed in TKA patients, which is thought to alter knee contact loads. A comprehensive understanding of the influence of surgical implantation and muscle recruitment strategies on joint contact mechanics is crucial to improve surgical techniques, increase implant longevity, and inform rehabilitation protocols. In this study, a detailed musculoskeletal model with a 12 degrees of freedom knee was developed to represent a TKA subject from the CAMS-Knee datasets. Using motion capture and ground reaction force data, a level walking cycle was simulated and the joint movement and loading patterns were estimated using a novel technique for concurrent optimization of muscle activations and joint kinematics. In addition, over 12′000 Monte Carlo simulations were performed to predict knee contact mechanics during walking, considering numerous combinations of implant alignment and muscle activation scenarios. Validation of our baseline simulation showed good agreement between the model kinematics and loading patterns against the in vivo data. Our analyses reveal a considerable impact of implant alignment on the joint kinematics, while variation in muscle activation strategies mainly affects knee contact loading. Moreover, our results indicate that high knee compressive forces do not necessarily originate from extreme kinematics and vice versa. This study provides an improved understanding of the complex inter-relationships between loading and movement patterns resulting from different surgical implantation and muscle coordination strategies and presents a validated framework towards population-based modelling in TKA.