This study evaluated the influence of distal implants angulation and framework material in the stress concentration of an All-on-4 full-arch prosthesis. A full-arch implant-supported prosthesis 3D model was created with different distal implant angulations and cantilever arms (30° with 10-millimeter cantilever; 45° with 10-millimeter cantilever and 45° with 6-millimeter cantilever) and framework materials (Cobalt–chrome [CoCr alloy], Yttria-stabilized tetragonal zirconia polycrystal [Y-TZP] and polyetheretherketone [PEEK]). Each solid was imported to computer-aided engineering software, and tetrahedral elements formed the mesh. Material properties were assigned to each solid with isotropic and homogeneous behavior. The contacts were considered bonded. A vertical load of 200 N was applied in the distal region of the cantilever arm, and stress was evaluated in Von Misses (σVM) for prosthesis components and the Maximum (σMAX) and Minimum (σMIN) Principal Stresses for the bone. Distal implants angled in 45° with a 10-millimeter cantilever arm showed the highest stress concentration for all structures with higher stress magnitudes when the PEEK framework was considered. However, distal implants angled in 45° with a 6-millimeter cantilever arm showed promising mechanical responses with the lowest stress peaks. For the All-on-4 concept, a 45° distal implants angulation is only beneficial if it is possible to reduce the cantilever’s length; otherwise, the use of 30° should be considered. Comparing with PEEK, the YTZP and CoCr concentrated stress in the framework structure, reducing the stress in the prosthetic screw.