Nanodroplet formation is important to achieve supersaturation of active pharmaceutical ingredients (APIs) in an amorphous solid dispersion. The aim of the current study was to explore how polymer composition, architecture, molar mass, and surfactant concentration affect polymer-drug nanodroplet morphology with the breast cancer API, GDC-0810. The impact of nanodroplet size and morphology on dissolution efficacy and drug loading capacity was explored using polarized light microscopy, dynamic light scattering, and cryogenic transmission electron microscopy. Poly(N-isopropylacrylamide-stat-N,N-dimethylacrylamide) (PND) was synthesized as two linear derivatives and two bottlebrush derivatives with carboxylated or PEGylated end-groups. Hydroxypropyl methylcellulose acetate succinate grade MF (HPMCAS-MF) and poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) were included as commercial polymer controls. We report the first copolymerization synthesis of a PVPVA bottlebrush copolymer, which was the highest performing excipient in this study, maintaining 688 μg/mL GDC-0810 concentration at 60 wt % drug loading. This is likely due to strong polymer-drug noncovalent interactions and the compaction of GDC-0810 along the PVPVA bottlebrush backbone. Overall, it was observed that the most effective formulations had a hydrodynamic radius less than 25 nm with tightly compacted nanodroplet morphologies.