The chapter discusses the current lack of effective targeted delivery systems for treating bone-related disorders, particularly bone cancers. It highlights the limitations of small organic molecules in clinical drugs, which have short circulation half-lives and require high doses, leading to severe side effects. The advent of nanotechnology has opened new avenues for targeted drug delivery, with calcium-based nanoparticle systems showing promise in modulating calcium metabolism and the bone microenvironment to inhibit disease progression. The review focuses on calcium-based nanoparticle systems and bisphosphonates (BPs) as both nano-drugs and nano-delivery systems for bone-targeted therapy. It also explores the use of biomarkers for targeting bone diseases and the development of new drug delivery systems. The chapter emphasizes the potential of bone-targeted nano-drug and nano-delivery systems to improve the treatment of bone-related diseases by delivering therapeutic agents directly to the affected sites, reducing side effects, and enhancing efficacy.The chapter discusses the current lack of effective targeted delivery systems for treating bone-related disorders, particularly bone cancers. It highlights the limitations of small organic molecules in clinical drugs, which have short circulation half-lives and require high doses, leading to severe side effects. The advent of nanotechnology has opened new avenues for targeted drug delivery, with calcium-based nanoparticle systems showing promise in modulating calcium metabolism and the bone microenvironment to inhibit disease progression. The review focuses on calcium-based nanoparticle systems and bisphosphonates (BPs) as both nano-drugs and nano-delivery systems for bone-targeted therapy. It also explores the use of biomarkers for targeting bone diseases and the development of new drug delivery systems. The chapter emphasizes the potential of bone-targeted nano-drug and nano-delivery systems to improve the treatment of bone-related diseases by delivering therapeutic agents directly to the affected sites, reducing side effects, and enhancing efficacy.