With 40% of approved drugs and 90% of drugs in the pipeline being insoluble in water, developing methods to formulate and deliver hydrophobic drugs becomes urgent but remains a challenge. A large range of nanoparticles have been developed to encapsulate hydrophobic drugs. However, drug loading is usually less than 10% or even 1%. Herein, we report the fabrication of core‐shell nanoparticles having exceptionally high drug loading up to 65% (drug weight/the total weight of drug‐loaded nanoparticles) and high encapsulation efficiencies (>99%) based on modular biomolecule templating. Bifunctional amphiphilic peptides are designed to not only stabilize hydrophobic drug nanoparticles but also induce biosilicification at the nanodrug particle surface thus forming drug‐core silica‐shell nanocomposites. This platform technology is highly versatile for encapsulating various hydrophobic cargos. Furthermore, the high drug loading nanoparticles lead to better in vitro cytotoxic effects and in vivo suppression of tumor growth, highlighting the significance of using high drug loading nanoparticles.