Background: Mesio–occluso–distal (MOD) cavity preparations are often fragile due to the amount of tooth and carious structure removed. MOD cavities can often fracture if left unsupported. Aim: The study investigated the maximum fracture load of mesi–occluso–distal cavities restored using direct composite resin restorations with various reinforcement techniques. Method: Seventy-two freshly extracted, intact human posterior teeth were disinfected, checked, and prepared according to predetermined standards for mesio–occluso–distal cavity design (MOD). The teeth were assigned randomly into six groups. The first group was the control group restored conventionally with a nanohybrid composite resin (Group I). The other five groups were restored with a nanohybrid composite resin reinforced with different techniques: the ACTIVA BioACTIVE-Restorative and -Liner as a dentin substitute and layered with a nanohybrid composite (Group II); the everX Posterior composite resin layered with a nanohybrid composite (Group III); polyethylene fibers called “Ribbond” placed on both axial walls and the floor of the cavity, and layered with a nanohybrid composite (Group IV); polyethylene fibers placed on both axial walls and the floor of the cavity, and layered with the ACTIVA BioACTIVE-Restorative and -Liner as a dentin substitute and nanohybrid composite (Group V); and polyethylene fibers placed on both axial walls and the floor of the cavity and layered with the everX posterior composite resin and nanohybrid composite (Group VI). All teeth were subjected to thermocycling to simulate the oral environment. The maximum load was measured using a universal testing machine. Results: The highest maximum load was exhibited by Group III with the everX posterior composite resin, followed by Group IV, Group VI, Group I, Group II, and Group V. A statistically significant difference was demonstrated between groups (p = 0.0023). When adjusting for multiple comparisons, there were statistical differences specific to comparisons between Group III versus I, Group III versus II, Group IV versus II, and Group V versus III. Conclusions: Within the limitations of the current study, it can be concluded that a higher maximum load resistance can be achieved (statistically significant) when reinforcing nanohybrid composite resin MOD restorations with everX Posterior.