In cells, intra- and intermolecular interactions of proteins confer function, and the dynamic modulation of this interactome is critical to meet the changing needs required to support life. Cross-linking and mass spectrometry (XL–MS) enable the detection of both intra- and intermolecular protein interactions in organelles, cells, tissues, and organs. Quantitative XL–MS enables the detection of interactome changes in cells due to environmental, phenotypic, pharmacological, or genetic perturbations. We have developed new informatics capabilities, the first to enable 3D visualization of multiple quantitative interactome data sets, acquired over time or with varied perturbation levels, to reveal relevant dynamic interactome changes. These new tools are integrated within release 3.0 of our online cross-linked peptide database and analysis tool suite XLinkDB. With the recent rapid expansion in XL–MS for protein structural studies and the extension to quantitative XL–MS measurements, 3D interactome visualization tools are of critical need.