Background: Atypical odontalgia (AO) is a poorly understood condition of orofacial pain and is often misdiagnosed. The pharmacological approach varies from case to case. This may be due to the differences in etiology, clinical symptoms, as well as comorbidities in each patient. Objective: This systematic review aimed at identifying and comprehending the adequate pharmacological approaches in AO management. Methods: In this systematic review, case reports that used pharmacological approach(es) as part of the AO management in the last 10 years (2010 to 2020) were reviewed using the PRISMA analysis guidelines. Initial screening was performed using keywords and inclusion criteria in several databases. Subsequently, further screening was carried out by checking for any duplication, followed by an assessment of the title and abstract and the entire content of the case report. All three authors were independently involved in studies selection based on the inclusion criteria, data extraction, and bias assessment. Results: Five hundred and ninety-five articles were identified from the initial search. The final result consisted of eleven case reports reviewed in this study. The use of antidepressants in AO management was reported in eight cases, anticonvulsants in five cases, antipsychotic in two cases, opioid analgesics in two cases, and topical analgesics in two cases. Conclusion: Based on this systematic review, various pharmacological agents showed adequate results as AO management. Antidepressants seemed to be the most effective ones (PROSPERO registration ID: CRD42021245918).