Delamination at heterogeneous metal/polymer interfaces during reliability testing of packaged devices continues to be a reliability issue in microelectronic packaging. Although interfacial adhesion properties are largely determined by molecular structures at buried interfaces, structure-property relationships at buried metal/polymer interfaces are not well understood due to a lack of nondestructive interface sensitive analytical techniques. In this paper, methodology was developed to nondestructively characterize the molecular structure at buried copper/epoxy interfaces in situ using infrared-visible sum-frequency generation (SFG) vibrational spectroscopy. The methodology was applied to elucidate the relationship between molecular structure at the buried copper/epoxy interface and delamination behavior by correlating molecular structure with the locus of failure analysis. SFG and locus of failure analysis suggest that molecular ordering and silane behavior at the copper interface both contribute to a gradient in network structure and mechanical properties near the copper interface which was correlated with a locus of failure at an interfacial weak zone. The combined destructive and nondestructive characterization methodology developed here is general and can be directly applied to selectively characterize relationships between molecular structure at buried metal/polymer interfaces and interfacial properties such as adhesion, delamination, and interfacial moisture transport during Joint Electron Device Engineering Council qualification testing.