Targeted drug delivery systems based on metal–organic frameworks (MOFs) have undergone tremendous progress and are widely applicable to diverse scientific fields. However, translating MOF agents directly into targeted drug delivery systems remains a challenge due to the biomolecular corona phenomenon. Here, we confirmed that supramolecular conjugation of antibodies to the surface of MOF particles by electrostatic interactions and coordination bonding can reduce protein adhesion in biological environments to show stealth shields. We confirmed that the pore size of MOF’s surface is critical to stabilize the antibody conjugation onto MOF nanoparticles. Once the antibodies stably conjugated to MOF particle, it was neither easily exchanged with nor covered by biomolecule protein, indicating stealth effect and an enhanced targeting ability both in in-vitro and in-vivo. Furthermore, by plugging multi-antibodies (dual and triple types), the resulting antibodies–MOF platform can target multiple cancer cell lines. This study provides insights into the use of “supramolecular antibody conjugation” as a promising method for developing MOF-based drug delivery systems.