Post-mastectomy pain syndrome (PMPS) is a syndrome broadly applied to the development of chronic pain after surgical breast intervention (i.e., lumpectomy and mastectomy). The incidence of PMPS is likely underreported, and this has contributed to a paucity of high-level evidence related to the treatment of the aforementioned condition. A drive to reduce the burden of opioid use has led to pain management physicians trialing a variety of strategies to help patients manage PMPS. This review discusses the latest evidence behind treatment options for PMPS, exploring medications as well as interventional techniques (e.g., nerve blocks, radiofrequency ablation, neuromodulation, and intrathecal drug delivery systems). Recent advances in neuromodulation technology are of particular interest here due to the well-localized nature of PMPS-related pain and the specificity with which modern neuromodulation techniques can generate an effect. Finally, the review proposes a framework with which to approach the care of patients with PMPS, with a specific emphasis on the early consideration of neuromodulation techniques along with functional and physical therapy to reduce patient medication burden and improve overall quality of life.