Bone metastasis is a common cause of death in patients with non-small cell lung cancer (NSCLC), with approximately 30-40% of NSCLC patients eventually developing bone metastases. Bone metastasis, especially the occurrence of skeletal-related events (SREs), significantly reduces overall survival (OS) and quality of life (QoL) in patients. Although bone-targeting agents (BTAs) have been shown to reduce SREs and improve QoL in NSCLC patients with bone metastases, the prognosis for these patients remains poor. Understanding the underlying molecular pathways of bone metastasis is crucial for the development of novel therapeutic approaches. Bone metastasis is a complex, multistep process that involves interactions between tumor cells and the bone microenvironment. The bone microenvironment provides a fertile soil for tumor cells, and crosstalk among various signaling pathways and secreted factors also plays a role in regulating the occurrence and progression of bone metastasis in NSCLC. In this article, we provide a comprehensive review of the process, regulatory mechanisms, and clinical treatment in NSCLC bone metastasis, with the hope of assisting with clinical treatment.