Purpose: To investigate causes, diagnostics and treatment modalities for persistent socket pain (PSP) after enucleation and evisceration. Methods: A systematic search was undertaken in accordance with the PRISMA Statement, in PubMed, Embase.com and Thomson Reuters/Web of Science. We searched for relevant papers until the 28th of July 2016. Inclusion criteria were (1) patients with a history of enucleation or evisceration, (2) PSP, (3) report of the cause and/or used diagnostics and/or treatment modality, (4) full text in English, Dutch or Spanish language. Excluded were (1) review articles, (2) comments, and publications concerning, (3) nonhumans, (4) exenterated patients, (5) acute postoperative pain, or (6) periorbital pain without pain in the socket. Given the lack of high quality evidence from randomized controlled trials, we examined all available evidence from primary observational studies and assessed quality within this lower level of evidence. Results: A total of 32 studies were included. Causes of PSP found were prosthesis-related (n = 5), dry socket (n = 2), trochleitis (n = 3), compression of the trigeminal nerve (n = 2), implant-related (n = unknown), inflammation (n = 5), surgery-related (n = 4), neuromas (n = 8), malignant tumours (n = 3), psychiatric/psychosocial (n = 2), phantom pain (n = 149), rarer entities (n = 3) or unknown (n = 14). Nonsurgical treatments suffice for conditions as trochleitis, prosthesis-related pain, dry socket and for phantom pain. Other causes of pain may require more invasive treatments such as implant removal. Conclusion: Careful history and examination can give some direction in the diagnostic procedure; however, PSP is probably multifactorial and the specific origin(s) may remain uncertain. Implant replacement can be an effective treatment. Studies to identifiy less invasive procedures are required.