Objective: To assess the prognostic factors for anatomic and hearing success after tympanoplasty in the setting of complex middle ear pathology. Methods: A systematic review was performed in January 2022. English-language articles describing outcome data for tympanoplasty repair variables including underlying pathology, perforation location, smoking status, graft technique, reconstruction material, anatomic success, and hearing success were extracted. Articles were included when tympanosclerosis, retraction pockets, adhesions, cholesteatoma, chronic suppurative otitis media, anterior perforations, and smoking were included. Underlying pathology, perforation location, smoking status, graft technique, reconstruction material, anatomic success, and hearing success were extracted. Any factors analyzed as potential indicators of success were sought out. Results: Data sources included PubMed, OVID, Cochrane, Web of Science, Scopus, and manual search of bibliographies. Ninety-three articles met final criteria, which accounted for 6685 patients. Fifty articles presented data on both anatomic and hearing outcomes, 32 articles presented data on anatomic outcomes only, and 11 articles presented data on hearing outcomes only. This systematic review found that adhesions and tympanosclerosis were prognostic factors for poorer hearing. Additionally, smoking and tympanosclerosis may be predictive of anatomic failure; however, the significance of this finding was mixed in included studies. This analysis is significantly limited by both the heterogeneity within the patients and the lack of controls. Conclusion: Adhesions and tympanosclerosis were prognostic factors for poorer hearing. Clearly documented methods and outcomes for the included pathologies could lead to more definitive conclusions regarding prognostic factors for success. Level of Evidence: 3B