Purpose: Material selection significantly impacts implant-supported fixed partial dentures (IS-FPDs) clinical performance. This study assessed and compared the marginal gap, screw loosening, and their relationship in 3-unit IS-FPDs. Materials and Methods: Fifty frameworks were fabricated from zirconia (Zir), chrome–cobalt (Co–Cr), titanium (Ti), polyetheretherketone (PEEK), and polyetherketoneketone (PEKK) (n=10 each) using CAD/CAM technology on a standardized two-implant model. Vertical marginal discrepancies were measured using scanning electron microscopy at four points per framework/abutment interface. Screw loosening was assessed using a digital torque device. Data were analyzed using SPSS with a significance level of P<0.05. Results: The marginal mean gap differed significantly between the groups across all four surfaces (P<.001). Overall, PEEK had the smallest gap (67.22 ± 15.55 μm), followed by Ti (105.65 ± 30.52 μm), PEKK (106.80 ± 34.58 μm), and Zir (115.62 ± 22.02 μm), with Co–Cr showing the largest (176.87 ± 88.34 μm). In screw loosening tests, PEKK demonstrated the lowest values in both molar (0.44% ± 0.73%) and premolar (0.06% ± 1.40%) abutments, whereas PEEK showed the highest values in molar (1.03% ± 1.21%) and Co–Cr in premolar (2.15% ± 1.29%) abutments. No significant correlation was observed between the marginal gap and screw loosening (P>.05). Conclusions: The findings of this study emphasize the critical role of material selection. PEEK offers superior marginal adaptation, potentially reducing microleakage, while PEKK enhances screw stability, minimizing prosthetic complications.