<p>Nanogels, of which the three-dimensional network structures are covalently crosslinked by crosslinkers and supported by large number of hydrogen bonds, present unique volume phase transition (VPT) and play significant roles in multiple biomedical applications. Based on hydrogen bonds, the VPT features including the shift, sharpness, and range of VPT, can be rationally designed and precisely controlled by simply regulating the monomer, comonomer, crosslinker, structure, deuteration, environmental stimuli, and so on, for tailored biomedical applications such as transcatheter arterial embolization (TAE) and tumor targeting drug delivery (TTDD). Moreover, the exploration of the minimum value of physicochemical properties around volume phase transition temperature (VPTT) exhibits great potential in improving current tumor therapies and developing more therapeutic strategies. Integrating systematic knowledge of nanogel VPT properties, we provide the guidance for rational design of nanogels with tailored biomedical applications.</p>