Despite showing promising functional outcomes for pelvic reconstruction after sarcoma resection, custom-made pelvic implants continue to exhibit high complication rates due to fixation failures. Patient-specific finite element models have been utilized by researchers to evaluate implant durability. However, the effect of assumed boundary and loading conditions on failure analysis results of fixation screws remains unknown. In this study, the postoperative stress distributions in the fixation screws of a state-of-the-art custom-made pelvic implant were simulated, and the risk of failure was estimated under various combinations of two bone-implant interaction models (tied vs. frictional contact) and four load cases from level-ground walking and stair activities. The study found that the average weighted peak von Mises stress could increase by 22-fold when the bone-implant interactions were modeled with a frictional contact model instead of a tied model, and the likelihood of fatigue and pullout failure for each screw could change dramatically when different combinations of boundary and loading conditions were used. The inclusion of additional boundary and loading conditions led to a more reliable analysis of fixation durability. These findings demonstrated the importance of simulating multiple boundary conditions and load cases for comprehensive implant design evaluation using finite element analysis.