Objectives: This study aimed to compare the clinical durability, mechanical performance, and stress behavior of three NiTi rotary systems—BlueShaper (Blue), BlueShaper Pro (Dual Wire), and BlueShaper Gold (fully gold-treated NiTi)—through a multimodal evaluation that included simulated instrumentation in 3D-printed replicas, mechanical testing, and finite element analysis (FEA). Methods: Sixty instruments (n = 20 per group) were tested. Simulated canal preparation was conducted in standardized 3D-printed mandibular molars with a 40° mesial root curvature until fracture occurred. Mechanical tests included torsional and flexural loading using a universal testing machine and stainless steel blocks with a standardized 40° curvature. FEA simulations evaluated von Mises stress, shear stress, total deformation, cyclic fatigue behavior, and contact pressure between the instrument and canal wall. Results: BlueShaper Gold prepared an average of 7.5 canals before fracture, followed by BlueShaper Pro (5.67 canals) and Blue (5.00 canals) (p < 0.001). Gold exhibited the highest torsional resistance (6.08 ± 3.08 N) and the longest fatigue life (325 ± 55.7 cycles), with the lowest von Mises stress and damage factor in FEA. BlueShaper Pro showed the longest time to fracture in mechanical testing (73.85 ± 7.10 s) and balanced mechanical behavior. Blue demonstrated the lowest performance across most parameters, including the shortest fatigue life and highest stress concentration. Conclusions: BlueShaper Gold exhibited the highest mechanical strength and fatigue resistance. BlueShaper Pro demonstrated the longest fatigue life and balanced mechanical behavior. Blue showed the lowest performance across most parameters. The strong correlation among clinical, mechanical, and FEA data reinforces the critical role of alloy composition in determining instrument durability, even when design remains constant.