Acute and chronic pain are recognized as the most recurrent and distressing symptoms of cancer, and cancer-related pain management can be challenging. Despite the complex nature of cancer pain, the activation of different ion channels and cannabinoid receptors, the increased production of growth factors, and the release of inflammatory mediators are implicated in the initiation and maintenance of cancer pain. All these factors can be considered promising potential targets for the development of novel pharmacotherapies useful in the treatment of many painful conditions, including cancer-related pain. Regardless of the source triggering the cancer-related pain, conventional therapy still relies on opioids and standard first- and second-line analgesics, leading to a considerable proportion of patients dealing with insufficient pain relief. Although the underlying mechanism of cancer pain remains unclear, recent studies proposed adopting a mechanism-based system, considering the differential classification of pain (nociceptive, neuropathic, or nociplastic pain) rather than the symptom-orientated classification frequently used with oncological patients. Looking into a more complex approach appears to be a promising pathway to be unraveled, leading to a better comprehension of the precise mechanisms responsible for mitigating this pain. Here, we focused on summarizing the established knowledge about the clinically available treatments and the emerging mechanisms under the scope of novel therapy options for relieving cancer pain.