The development and application of multiscale modeling and simulation techniques are increasingly desirable for investigating assemblies of molecular nanoparticles having various geometries and/or functionalized with various substituents. The development of a coarse-grained force field for accurately simulating polymer-tethered polyhedral oligomeric silsesquioxane (POSS) nanoparticle self-assembly in a common organic solvent will be presented here. The force field consists of effective solvent-mediated interaction potentials that already account for POSS-solvent molecule interactions. The coarse-graining approach used is a structural-based one where effective numerical potentials are derived that reproduce in the coarse-grained simulations target structural properties in the underlying atomistic simulations. In simulations of self-assembly, various types of local packings of the POSS cages and tether conformations are observed in the atomistic simulations and sufficiently captured in the coarse-grained model. The coarse-grained force field affords a savings of about two orders of magnitude in computing time. In addition to obtaining the solvent-mediated effective potentials for simulating POSS molecule self-assembly, particular aspects of the coarse-graining approach, including nonuniqueness of the effective potentials and variations on the numerical iteration algorithm, are examined.