AbstractOwing to low drug delivery efficiency (<1%), nanoparticle‐based drug delivery system remains great challenge for efficient tumor chemotherapeutics. In this study, bioinspired coordination‐assembled nanoparticles (CuET@HR‐Pro) are fabricated by programming the assembly of three types of functional biomolecules (heparin, cRGD, and protamine) and the anti‐cancer drug (CuET). The nanoparticles enhanced the drug delivery efficiency of an intravenous injective dose to up to 6.9%, and thereby significantly improving the anti‐tumor efficacy of the drug. The CuET@HR‐Pro is fabricated by patching coordination‐assembled CuET@heparin‐cRGD (CuET@HR) nanoparticles onto the surface of protamine (Pro) nanoparticles in 10% fetal bovine serum. The enhanced drug delivery capacity of the obtained CuET@HR‐Pro nanoparticles is due to their improved stability (anti‐complement activation, anti‐protein adhesion), targeting capacity, and cell penetration ability. As expected, CuET@HR‐Pro exhibited a superior inhibitory effect on orthotopic ovarian cancer in nude mice. The proposed strategy provides an alternative for achieving highly efficient drug delivery and tumor therapy.