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Their endogenous biogenesis pathways provide unique opportunities to regulate cargo selection through both environmental modulation and genetic programming. This review outlines how EV\u2010producing cells can be reprogrammed to load functional proteins and nucleic acids by combining environmental cues with genetic modifications that leverage intrinsic sorting machinery and engineered molecular interactions. For protein cargo, we outline strategies that reshape EV composition through physiological stimuli, as well as genetically encoded systems designed to recruit proteins via scaffold fusion, peptide tags, or fusion\u2010independent mechanisms. For nucleic acid cargo, we highlight approaches that leverage environment\u2010driven alterations in RNA abundance, together with targeted loading methods that rely on scaffold\u2010RNA\u2010binding proteins (RBPs) fusion constructs, natural sorting motifs, and sorting\u2010related RBPs to enrich miRNAs, mRNAs, and ribonucleoprotein complexes. 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