Diseases are a manifestation of how thousands of proteins come together to form cell- and tissue-specific networks. Understanding these networks holds a key to diagnosing and treating diseases. These protein-protein interaction (PPI) networks are context dependent, and thus require systems level assessment to study, but tools for identification, analysis, and modulation of whole proteomes are lacking. So, a research team recently used reagents that bind epichaperomes, which are maladaptive scaffolding structures and developed an epichaperome-based ‘omics platform, epichaperomics, to identify disease-related PPI alterations. Several lines of evidence demonstrated that these probes could provide important mechanistic and therapeutic proteome-wide insights. Applying the epichaperomics platform to the PPI dysfunctions in cancer cells provided proof-of-principle and enabled the discovery of a context-dependent mechanism where cancer cells enhance the fitness of mitotic protein networks. Although more research is needed, epichaperomics could lead to novel therapeutics that normalize PPI networks using epichaperome chemical binders and can help uncover disease mechanisms previously undetected by conventional ‘omics approaches.