<p>Hydroxyapatite nanoparticles (HANPs) have emerged as versatile and biocompatible platforms in cancer nanomedicine, offering multifunctional roles in drug delivery, imaging, and combinatorial therapy. Their structural similarity to bone apatite, tunable surface chemistry, and ion substitution capability enable precise functionalization for targeted and sustained drug release. This review provides a comprehensive overview of HA-mediated combinatorial cancer therapies, emphasizing their role as drug carriers, photothermal agents, and immunomodulators. The integration of HANPs with chemotherapeutic drugs, immunotherapy, photothermal and photodynamic therapy, and trace-element doping has shown significant synergistic effects enhancing antitumor efficacy while minimizing systemic toxicity. Furthermore, HANPs have demonstrated promise as theranostic agents by combining therapeutic and diagnostic functions through multimodal imaging techniques, including MRI, fluorescence, and PET/SPECT. Collectively, these advances underscore HANPs as intelligent, biocompatible nanoplatforms capable of simultaneous diagnosis and therapy. Despite remarkable preclinical progress, future studies must address scalability, long-term biosafety, and clinical translation to realize their potential in precision oncology fully.</p>