Introduction: Peripheral nerve injuries (PNIs) resulting from trauma or surgery can lead to neuropathic pain and, in some cases progress to centralized pain. This condition significantly affects patients’ quality of life and functional abilities. However, diagnostic criteria for centralized pain after PNI remain poorly defined, complicating patient identification and treatment. This systematic review aimede to assess current diagnostic approaches and propose evidence-based criteria for clinical diagnosis. Methods: A systematic search of MEDLINE, Embase, Web of Science, and CENTRAL was conducted for studies assessing diagnostic approaches for centralized pain after PNI. Included studies addressed clinical characteristics, diagnostic tests, or signs of centralized pain after PNI. Exclusion criteria included acute pain studies (<3 mo), pediatric patients, and non-English articles. Results: From 950 citations screened, 28 studies (6189 patients) were included. On the basis of the synthesized evidence, we propose the following diagnostic criteria for centralized pain after PNI: (1) documented peripheral nervous system injury or compression; (2) neuropathic pain persisting for 3 months; (3) hyperalgesia, allodynia, or other forms of hypersensitivity extending beyond the primary zone of injury; (4) associated mood/cognitive disturbances; and (5) limited response to peripheral nerve blocks, defined as <50% pain reduction, if performed. Conclusions: This study proposes a comprehensive, evidence-based diagnostic framework for centralized pain after PNI. The algorithm combines clinical criteria with optional diagnostic testing, providing a practical approach for diagnosis that accounts for variability in access to advanced diagnostic tools. By standardizing the diagnostic process, the framework aims to enhance patient identification and support appropriate treatment selection in clinical practice. Level of Evidence: Level III—systematic reviews.