In-situ nanoindentation experiment has been widely adopted to characterize material behaviors of microelectronic devices. This work introduces the latest developments of nanoindentation experiment in characterizing nonlinear material properties of 3D integrated microelectronic devices with through-silicon-vias (TSVs). The elastic, plastic, and interfacial fracture behavior of the copper via and matrix-via interface have been characterized using small scale specimens prepared with focused-ion-beam (FIB) and nanoindentation experiment. A brittle interfacial fracture was found at the Cu/Si interface under mixed-mode loading with a phase angle ranging from 16.7 to 83.7 degrees. The mixed-mode fracture strengths were extracted using the linear elastic fracture mechanics (LEFM) analysis and a fracture criterion was obtained by fitting the extracted data with the power-law function. The vectorial interfacial strength and toughness were found to be independent with mode-mix.