A new heparin targeting delivery platform was developed based on iron oxide (Fe3O4) nanoparticles and polyethyleneimine (PEI) functionalized black phosphorus nanosheets (BP NSs). Both in and ex vivo studies suggested that this drug delivery platform (PEI/Fe3O4@BP NSs) possessed high heparin loading capacity (≈450%), accurate magnetic enrichment capacity, and good biocompatibility. With the aid of near-infrared (NIR) laser irradiation, this BP NS based delivery platform could further enhance the photothermal thrombolysis effect. Most importantly, the experiments in vivo confirmed that the proposed PEI/Fe3O4@BP NSs could considerably prolong the effective drug concentration duration of heparin. By which means, accurate, long-acting, and effective thromboprophylaxis could be accomplished with limited drug dosage, which could radically reduce the perniciousness of drug overdose.