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This work was supported by Erciyes University Research Project Fund (BAP-FDK-20188555) to S.O. We are grateful to Turkey Council of Higher Education for supporting M. Burak Acar with the CoHE 100/2000 Doctoral Scholarship Project. This work was partially supported by Regione Campania Progetto POR "Sviluppo di nanotecnologie Orientate alla Rigenerazione e Ricostruzione tissutale, Impiantologia e Sensoristica Odontoiatria/oculistica-SORRISO" CUP B23D18000250007 to G.P. and U.G. This was partially supported by Life Science Institute Inc., Tokyo, Japan to U.G. for a Joint Re-search Agreement. Muse cells are adult stem cells that are present in the stroma of several organs and possess an enduring capacity to cope with endogenous and exogenous genotoxic stress. In cell therapy, the peculiar biological properties of Muse cells render them a possible natural alternative to mesenchymal stromal cells (MSCs) or to in vitro-generated pluripotent stem cells (iPSCs). Indeed, some studies have proved that Muse cells can survive in adverse microenvironments, such as those present in damaged/injured tissues. We performed an evaluation of Muse cells' proteome under basic conditions and followed oxidative stress treatment in order to identify ontologies, pathways, and networks that can be related to their enduring stress capacity. We executed the same analysis on iPSCs and MSCs, as a comparison. The Muse cells are enriched in several ontologies and pathways, such as endosomal vacuolar trafficking related to stress response, ubiquitin and proteasome degradation, and reactive oxygen scavenging. In Muse cells, the protein-protein interacting network has two key nodes with a high connectivity degree and betweenness: NFKB and CRKL. The protein NFKB is an almost-ubiquitous transcription factor related to many biological processes and can also have a role in protecting cells from apoptosis during exposure to a variety of stressors. CRKL is an adaptor protein and constitutes an integral part of the stress-activated protein kinase (SAPK) pathway. The identified pathways and networks are all involved in the quality control of cell components and may explain the stress resistance of Muse cells. Erciyes University Research Project Fund BAP-FDK-20188555 Turkey Council of Higher Education CoHE 100/2000 Doctoral Scholarship Project Regione Campania Progetto POR "Sviluppo di nanotecnologie Orientate alla Rigenerazione e Ricostruzione tissutale, Impiantologia e Sensoristica Odontoiatria/oculistica-SORRISO" CUP B23D18000250007 Life Science Institute Inc., Tokyo, Japan