Manufactured nanomaterials (MNMs) are rapidly being incorporated into a wide variety of commercial products with significant potential for environmental release, which calls for eco-responsible design and disposal of nanoenabled products. Critical research needs to advance this urgent priority include (1) structure-activity relationships to predict functional stability and chemistry of MNMs in the environment and to discern properties that increase their bioavailability, bioaccumulation, and toxicity; (2) standardized protocols to assess MNM bioavailability, trophic transfer, and sublethal effects; and (3) validated multiphase fate and transport models that consider various release scenarios and predict the form and concentration of MNMs at the point of exposure. These efforts would greatly benefit from the development of robust analytical techniques to characterize and to track MNMs in the environment and to validate models and from shared reference MNM libraries.