Highly cross-linked polymers are extensively used in the formulation of protective coatings, adhesives, and composite materials. The inherent densely cross-linked structure makes these materials strong but brittle limiting their use. This investigation reveals that rearranging the molecular structure of these polymers can significantly improve toughness without degrading and sometimes even enhancing other essential thermal and mechanical properties. Epoxy polymers are synthesized such that they have the same overall chemical composition but different molecular arrangements. These systems are referred to as polymer network isomers. The structural variations are introduced by using a processing technique termed "partially reacted substructures (PRS)". The PRS were made from the stoichiometric reactions of poly(propylene oxide)diamine and diglycidyl ether of bisphenol A (DGEBA) up to specified extents of reaction (0, 60, 70, and 80%). The resulting still reactive PRS were mixed and cured with stoichiometric blends of DGEBA and diethyltoluenediamine at specified PRS contents (10, 15, and 20 wt %). The polymer isomers are those with the same PRS content and different PRS chemical conversion. At the same PRS loading, compact tension results indicated a remarkable improvement in fracture toughness (G(1c)) with increasing PRS conversion. SEM micrographs indicated the presence of voids on the fracture surfaces of the modified samples. Cavitation-induced shear deformation was found to be responsible for increasing fracture toughness in PRS-modified systems. Small-angle X-ray scattering results revealed the existence of heterogeneous nanodomains with domain sizes that were directly proportional to PRS conversion. Additionally, quasi-static tension tests showed that mechanical properties such as Young's modulus and strength were almost invariant for a given set of network isomers. It was also observed that the glass transition temperature (T-g) of the modified systems was higher than those of the corresponding control systems, thus resulting in materials with both improved fracture toughness and T-g. In summary, polymer network isomers with improved thermal and mechanical properties are obtained by rearranging the network molecular structures via the addition of a single processing step. These findings can be directly and economically applied to current industrial coating, adhesive, and composite formulations.