In this feature article, we summarize our recent work on understanding and controlling the thermal behavior of nanoparticles grafted with thermoresponsive polymer shells. Precision synthesis of monodisperse superparamagnetic iron oxide nanocrystals was combined with irreversible dense grafting of nitrodopamide-anchored thermoresponsive polymer chains. We provide an overview of how the dense and stable grafting of biomedically relevant polymers, including poly(ethylene glycol), poly( N-isopropylacrylamide), polysarcosin, and polyoxazolines, can be achieved. This platform has made it possible for us to demonstrate that the polymer brush geometry, as defined by the nanoparticle core and relative polymer brush size, determines the thermal transitions of the polymer brush. We furthermore summarize our work on how the polymer shell transitions and nanoparticle aggregation can be tuned. With the independent variation of the core and the shell, we can optimize and precisely control the thermally controlled solubility of our system. Finally, our feature article gives examples relevant to current and future applications. We show how the thermal response of the shell influences the nanoparticle performance in biological fluids and interactions with proteins and cells, also under purely magnetic actuation of the nanoparticles through the superparamagnetic iron oxide core.