Methadone & Oxycodone are both very powerful for opioid pain medications used for severe chronic pain and cancer-related pain. Methadone is often preferred for chronic, neuropathic, or cancer pain due to its long action. Oxycodone is often preferred for acute pain and breakthrough pain because it is available in a fast-acting formulation. Methadone has multiple metabolites that accumulate during the first two weeks of treatment no matter dose of the drug.