A monolith bonding system has a high reliability for dissimilar material bonding. The epoxy monolith layer fabricated on a substrate guarantees bond strength by the anchor effect, regardless of the compatibility of the used materials. Designing a high-performance monolith bonding system requires the suppression of an interfacial failure between the monolith and the substrate. In this study, silane and phosphine coupling agents containing amino and epoxy groups were used to construct a robust interfacial structure between the monolith and the substrates such as glass and metals. The internal and interfacial monolith structures were characterized by three-dimensional X-ray imaging as a nondestructive observation method in addition to the scanning electron microscopy of the sample cross sections. The modification of the substrate−monolith interface using the coupling agents improved the strength of dissimilar material bonding of the glass and metal substrates in combination with thermoplastic resins such as poly(ethylene terephthalate) and polycarbonate bisphenol-A.