Abstract: To address the weak interfacial bonding and limited toughening efficiency of insoluble thermoplastic microparticles in highly crosslinked epoxy resin (EP), polyamide (PA) microparticles were surface-modified through the in situ deposition of polydopamine (PDA) to fabricate PDA-coated PA (PA@PDA) core–shell microparticles, which were subsequently incorporated into an epoxy resin matrix. The effects of PA@PDA core–shell microparticles on the mechanical properties, thermal properties, rheological behavior, and fracture morphology of the epoxy resin were systematically investigated. The results showed that PDA was successfully deposited onto the surfaces of the PA microparticles. The PA@PDA microparticles promoted the curing reaction of the epoxy resin, reducing the apparent curing activation energy to 77.34 kJ/mol. The incorporation of PA@PDA had no adverse effect on the thermomechanical properties or rheological behavior of the epoxy resin. The incorporation of PA@PDA increased the storage modulus in the glassy region while maintaining the glass transition temperature (Tg). Meanwhile, the complex viscosity of the PA@PDA-modified epoxy system remained in the same order of magnitude as that of neat EP within the low-viscosity processing region. The PA@PDA core–shell microparticles significantly improved the fracture toughness of the epoxy resin. At a PA@PDA content of 15wt.%, the tensile strength was maintained at 89.82 MPa, while the fracture toughness reached 1.32 MPa·m¹/², representing an increase of 69.2% compared with neat EP. Fractographic analysis revealed that the PA@PDA-modified epoxy system exhibited a markedly rougher fracture surface, together with pronounced crack deflection and branching, indicating that the toughening effect was primarily attributed to crack deflection, crack branching, and enhanced energy dissipation during fracture. This work demonstrates that the design of PA@PDA core–shell microparticles enables the efficient toughening of highly crosslinked epoxy resin using insoluble thermoplastic microparticles and provides a reference for interfacial engineering and toughening modification of high-performance epoxy resin systems.