The article discusses the complex interactions between cancer cells and the bone microenvironment, which are crucial for the development and progression of bone metastases. When cancer spreads to the bones, it leads to significant pain and deregulated bone remodeling, significantly reducing the chances of a cure. The bone microenvironment, composed of osteoclasts, osteoblasts, and other cells, is essential for tumor growth and invasion. Understanding the components of this environment and the factors that modulate them is key to developing therapeutic strategies. Bisphosphonates and RANKL inhibitors are currently used to suppress bone resorption and reduce skeletal complications, but they do not always prevent new metastases. Emerging data suggest that these anti-resorptive agents may also have direct antitumor effects. The article highlights the importance of targeting the bone microenvironment, including osteoclasts, osteoblasts, immune cells, and the bone matrix, to prevent and treat bone metastases. It also discusses the role of WNT signaling, pre-metastatic niches, and the interaction between tumor cells and bone marrow stromal cells in the process of bone colonization. Additionally, the article explores the therapeutic potential of targeting TGFβ signaling, bone matrix proteins, and neoangiogenesis. Finally, it emphasizes the need for better animal models and advanced technologies to further our understanding of bone metastasis and to develop more effective treatments.The article discusses the complex interactions between cancer cells and the bone microenvironment, which are crucial for the development and progression of bone metastases. When cancer spreads to the bones, it leads to significant pain and deregulated bone remodeling, significantly reducing the chances of a cure. The bone microenvironment, composed of osteoclasts, osteoblasts, and other cells, is essential for tumor growth and invasion. Understanding the components of this environment and the factors that modulate them is key to developing therapeutic strategies. Bisphosphonates and RANKL inhibitors are currently used to suppress bone resorption and reduce skeletal complications, but they do not always prevent new metastases. Emerging data suggest that these anti-resorptive agents may also have direct antitumor effects. The article highlights the importance of targeting the bone microenvironment, including osteoclasts, osteoblasts, immune cells, and the bone matrix, to prevent and treat bone metastases. It also discusses the role of WNT signaling, pre-metastatic niches, and the interaction between tumor cells and bone marrow stromal cells in the process of bone colonization. Additionally, the article explores the therapeutic potential of targeting TGFβ signaling, bone matrix proteins, and neoangiogenesis. Finally, it emphasizes the need for better animal models and advanced technologies to further our understanding of bone metastasis and to develop more effective treatments.