State-of-the-art three-dimensional very large-scale integration (3D-VLSI) relies, among other factors, on the purity of high-aspect-ratio Cu interconnects such as through-silicon-vias (TSVs). Accurate spatial chemical analysis of electroplated TSV structures has been proven to be challenging due to their large aspect ratios and their multimaterial composition (Cu and Si) with distinct physical properties. Here, we demonstrate that these structures can be accurately analyzed by femtosecond (fs) laser beam ablation techniques in combination with ionization mass spectrometry (LIMS). We specifically report on novel preparation approaches for the postablation analysis of craters formed upon TSV depth profiling. The novel TSV sample preparation is based on deep and material-selective reactive-ion etching of the Si matrix surrounding the Cu interconnects thus facilitating systematic focused-ion-beam (FIB) investigations of the high-aspect-ratio TSV structures upon ablation. The particular structure of the TSV analyte combined with the beam > Cu-TSV condition allowed for an in-depth investigation of fundamental laser ablation processes, particularly focusing on the redeposition of ablated material at the inner side-walls of the LIMS craters. This phenomenon is of imminent importance for the ultimate quantification in any laser ablation-based depth profiling. In addition, we have developed a new method which allows the unambiguous determination of the crossing-point of the Si/Cu||bare Si interface upon Cu-TSV depth profiling which is based on pronounced, depth-dependent changes in the mass-spectrometric detection of those Sixy+ species formed upon the LIMS depth erosion.