A diverse array of nanomaterials ranging from polymer assemblies to nanoparticles has been under development for biomedical applications in recent years. A key aspect of these applications is the ability to target the materials to the desired locations in vivo by exploiting their size or through the conjugation of active targeting groups. While nanoscale scaffolds may provide advantages such as the multivalent presentation of targeting ligands, the binding of these ligands may also be inhibited by interfering polymer chains at their surfaces. This aspect was investigated here by preparing poly(butadiene-block-ethylene oxide) vesicles and dextran-coated iron oxide nanoparticles functionalized with dendritic and nondendritic displays of mannose, a well-known multivalent ligand. The binding of these systems to the mannose-binding protein Concanavalin A was compared using a hemagglutination assay. It was found that the dendritic systems exhibited 1-2 orders of magnitude enhancement in binding affinity relative to the nondendritic displays. This result is attributed to the ability of the dendritic groups to overcome steric inhibition by polymer chains at the material surface and also to the presentation of ligands in localized clusters. It is anticipated that these results should be applicable to a wide range of nanomaterials with polymers at their surfaces and that the method by which biological ligands are conjugated to the surfaces of nanoparticles and polymer assemblies should be carefully considered.