The present work investigates the effect of modifying an epoxy resin using two different modifiers. The mechanical and thermal properties were evaluated as a function of modifier type and content. The structure and morphology were also analyzed and related to the measured properties. Polyurethane (PUR) was used as a liquid modifier, while Cloisite Na+ and Nanomer I.28E are solid nanoparticles. Impact strength (IS) of hybrid nanocomposites based on 3.5 wt% PUR and 2 wt% Cloisite or 3.5 wt% PUR and 1 wt% Nanomer was maximally increased by 55% and 30%, respectively, as compared to the virgin epoxy matrix, exceeding that of the two epoxy/nanoparticle binaries but not that of the epoxy/PUR binary. Furthermore, a maximum increase in IS of approximately 20% as compared to the pristine matrix was obtained with the hybrid epoxy nanocomposite containing 0.5 wt% Cloisite and 1 wt% Nanomer, including a synergistic effect, due most likely to specific interactions between the nanoparticles and the epoxy matrix. The addition of polyurethane and nanoclays increased the thermal stability of epoxy composites significantly. However, DSC results showed that the addition of flexible polyurethane chains decreased the glass transition temperatures, while the softening point and the service temperature range of epoxy nanocomposites containing nanofillers were increased. FTIR analysis confirmed the occurrence of interaction between the epoxy matrix and added modifiers. All SEM micrographs showed significant roughness of the fracture surfaces with the formation of elongated platelets, explaining the increase in mechanical properties of the epoxy matrix.