This study evaluated the supramolecular properties of a new family of water-soluble hyperbranched polytriazoles that have a unimolecular micelle structure. Two new, structurally related hyperbranched polymers (HBPa and HBPn), with the same size (Dh = 11 nm) and core-shell architecture, were prepared and found to act as nanoscale hosts for a broad spectrum of molecular guests. The globular-shaped hyperbranched polymers were synthesized by a straightforward one-pot polymerization method that permits easy synthetic control of the multiple functional groups within the core. Surrounding the core is a shell of polyethylene glycol chains that promotes solubility in pH 7.4 buffer solution and inhibits self-aggregation of the nanoparticles. The core of HBPa, containing a mixture of anionic carboxylate groups and 1,2,3-triazole rings, could be loaded with cationic hydrophilic (i.e., propidium iodide) or partially hydrophobic (i.e., Hoechst 33342) dyes or drugs, including a binary dye/drug pair (i.e., indocyanine green/mitoxantrone). The core of HBPn, containing a mixture of uncharged 2-pentanone chains and 1,2,3-triazole rings, could be loaded with uncharged and very hydrophobic dyes (i.e., Nile Red) or drugs. Improved aqueous solubility of camptothecin was achieved 10-fold from 8.4 to 75 ng/mL. Additionally, cell toxicity studies showed that HBPn was able to release the camptothecin drug inside A549 cancer cells resulting in increased cell death. Taken together, the results suggest that this new family of water-soluble hyperbranched polytriazoles could be broadly useful as nanocarriers for various applications in therapy, imaging, or a combination of the two (theranostics).