Background. Metastatic progression is shaped by clonal dissemination, Darwinian selection, and subclonal diversification. Yet multiregion genomic analyses reveal substantial divergence between primary tumors and metastatic lesionsincluding high burdens of private mutations and organ-adapted transcriptional programsthat invite exploration of complementary mechanisms.&nbsp; <div> Results. We propose Exosome-Mediated Metastatic Transformation (EMMT), a hypothesisgenerating framework in which tumor-derived exosomes act as systemic carriers of oncogenic state information. We integrate three converging mechanisms: integrin-directed organotropic delivery of exosomal cargo, prion-like conformational templating of mutant p53, and LINE-1 retrotransposon-associated genomic instability. Together, these processes may contribute to local malignant reprogramming of distant tissues under permissive conditions, complementing classical clonal dissemination.&nbsp; </div> <div> Conclusions. EMMT is mechanistically plausible and experimentally testable, but currently lacks definitive in vivo, lineage-controlled validation. We outline key experimental predictionsincluding lineage-independent clone emergence, in vivo conformational templating, and horizontal LINE-1 insertions in recipient cellsand identify pharmacological entry points for future investigation. Rigorous lineage tracing combined with single-cell multi-omics will be required to determine whether exosome-mediated oncogenic transfer represents a biologically meaningful contributor to metastatic initiation. </div>