Interdisciplinary investigation at the interface of chemistry, engineering, and medicine has enabled the development of self-assembled nanomaterials with novel biochemical and electro-optical properties. We have recently shown that emissive polymersomes, polymer vesicles incorporating porphyrin-based fluorophores, feature large integrated-emission oscillator strengths and narrow emission bands; these nanoscale assemblies can be further engineered to fluoresce at discrete wavelengths throughout the visible and near-infrared (NIR) spectral domains. As such, emissive polymersomes effectively define an organic-based family of soft-matter quantum-dot analogs that possess not only impressive optical properties, but also tunable physical and biomaterial characteristics relative to inorganic fluorescent nanoparticles. Here, we expand upon our initial studies on poly(ethyleneoxide)-block-poly(butadiene)-based vesicles to examine fluorophore membrane-loading in other polymersome systems. Through modulation of fluorophore ancilliary group substituents and choice of polymer chain chemistries, we are able to predictably control intramembranous polymer-fluorophore interactions; these phenomena, in turn, influence the nature of fluorophore solvation, local dielectric environment, and emission quantum yield within emissive polymersome assemblies. By utilizing different classes of vesicle-generating diblock copolymers, including bioresorbable poly(ethyleneoxide)-block-poly(ε-caprolactone) (PEO-b-PCL) and poly(ethyleneoxide)-block-poly(γ-methyl-ε-caprolactone) (PEO-b-PMCL), we ascertain general principles important for engineering nanoscale optical vesicles. Further, this work heralds the first generation of fully biodegradable fluorescent nanoparticles suitable for deep-tissue in vivo imaging.