We detail the accuracy and validity of AI in diagnostic and prognostic models and biofluid markers that provide insight into AMD pathogenesis and progression. This review was conducted in accordance with the Preferred Reporting Items for a Systematic Review and Meta-analysis guidelines. A comprehensive search was conducted across 5 electronic databases including Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, EMBASE, Medline, and Web of Science from inception to July 14, 2021. Studies pertaining to biofluid marker analysis using AI or bioinformatics in AMD were included. Identified studies were assessed for risk of bias and critically appraised using the Joanna Briggs Institute Critical Appraisal tools.