The current trend in the global advanced material market is expeditiously shifting towards more lightweight, multifunctional configurations, considering very recent developments in electrical aircraft, biomedical devices, and autonomous automobiles. Hence, the development of novel polymer nanocomposite materials is critical to advancing the current state-of-the-art of structural material technologies to address the pressing performance demands. Aiming at expanding the existing material design space, we have investigated crosslinkable aromatic polyester matrix nanocomposites. Aromatic polyesters, in the thermosetting form, are a prospective high-performance/high-temperature polymer technology, which is on a par with conventional epoxy-derivative resins and high-performance engineering thermoplastics in the range of their potential applications. The aromatic matrix-based thermosetting nanocomposites manifest greatly enhanced physical properties enabled by a chemistry-favored robust interfacial covalent coupling mechanism developed during the in situ polymerization reaction with various nanofiller particle configurations. Here, we provide a summary review of our recent efforts in developing this novel polymer nanocomposite material system. We highlight the chemical strategy, fabrication approach, and processing techniques developed to obtain various nanocomposite representations for structural, electrical, optical, biomedical, and tribological applications. The unique characteristic features emerging in the nanocomposite morphologies, along with their physicochemical effects on the multifunctional macroscale properties, are demonstrated. This unique matrix configuration introduces superior performance elements to polymer nanocomposite applications towards designing advanced composite materials.