Osteomyelitis (OM), a debilitating disease caused by a microbial infection of the bones, continues to pose a formidable obstacle for orthopedic surgeons. The conventional methods for the prevention and treatment of OM are insufficient. In this research work, we developed a strategic green nanostructure using the antifungal drug Fluconazole (FCZ)‐assimilated zinc oxide nanoparticles (ZnO‐NPs) and hydroxyapatite (HAp) nanostructures as filler and hydrophobic polycaprolactone (PCL) as matrix by a solution‐based chemical method. The ceramic carrier‐like nanostructures ZnO and HAp were synthesized by the in situ precipitation method. The physicochemical characterization of the prepared polymer‐coated drug ceramic nanocomposite (FCZ‐ZnO‐HAp‐PCL) was achieved using Fourier transform infrared spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM), particle size distribution (PSD), X‐ray diffraction (XRD), and Energy‐dispersive X‐ray (EDX) analysis. Furthermore, the biocompatibility and anticancer activity of the nanocomposite were explored by an MTT assay study. Successfully synthesized FCZ‐ZnO‐HAp‐PCL nanocomposite exhibited profound antimicrobial activity against targeted microbe species and potential cytotoxicity towards MCF‐7 human breast adenocarcinoma cell lines, which may be potentially used for the treatment of OM and prospective infections.