Inclusion Criteria:  Have a participant-reported history of dry eye for at least 6 months prior to Visit 1 Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1 Have a best-corrected visual acuity (BCVA) of 0.7 minimum angle of resolution (logMAR) or better (Snellen equivalent score of 20/100 or better) in each eye at Visit 1 Report a score of ≥ 2 according to the Ora Calibra® ocular discomfort & 4-symptom questionnaire in at least one of the dry eye symptoms at Visits 1 and 2 Have a Schirmer's Test score of ≤ 10 mm and ≥ 1 mm in at least one eye at Visits 1 and 2 Have a corneal fluorescein staining score ≥ 2 according to the Ora Calibra® corneal and conjunctival staining scale for grading of fluorescein staining in at least 1 of the corneal regions (inferior, superior, or central) in at least 1 eye at Visits 1 and 2 Have a conjunctival redness score ≥ 1 according to the Ora Calibra® conjunctival redness for dry eye scale in at least 1 eye at Visits 1 and 2  Exclusion Criteria:  Have any clinically significant slit lamp findings at Visit 1 that may include active blepharitis, meibomian gland dysfunction, lid margin inflammation or active ocular allergies that require therapeutic treatment, and/or in the opinion of the investigator may interfere with study parameters Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1 Have worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the study Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 12 months Have used any cyclosporine-containing drops (such as Restasis®, Cequa®), or lifitegrast ophthalmic solution (Xiidra®) within 60 days of Visit 1 Have any previous experience using tanfanercept ophthalmic solution Be currently taking any topical ophthalmic prescription (including medications for glaucoma) or over-the-counter (OTC) solutions, artificial tears, gels or scrubs, and cannot discontinue these medications for the duration of the trial (excluding medications allowed for the conduct of the study) Be a woman who is pregnant, nursing or planning a pregnancy