Chronic pain imposes incalculable health and economic burdens, affecting more than 30% of the global population in published studies. Optimal management of chronic pain is imperative for individuals experiencing such distress. Nevertheless, the current approaches to chronic pain assessment and treatment fail to meet clinical requirements. In recent years, there has been a growing recognition of the need for precision medicine approaches to effectively manage chronic pain. Chronic pain can be classified into three categories: nociceptive (resulting from tissue injury), neuropathic (caused by nerve injury), or nociplastic (arising from a sensitized nervous system). These classifications significantly impact the evaluation and treatment decisions at all levels. Significantly, in practice, there is substantial overlap in chronic pain mechanisms among patients and within different types of chronic pain. The application of precision medicine is imperative in the management of chronic pain. This review offers a comprehensive overview of the distinctive molecular mechanisms underlying nociceptive, neuropathic, and nociplastic pain, including immune responses, ion channels, monoaminergic imbalance, and neuroinflammation. Subsequently, we summarized the status quo of nociceptive, neuropathic, and nociplastic pain manipulation. Last, we explored the advances in pain management strategies for chronic pain that are making significant progress toward their clinical implementation.