We report a case of chronic sympathetic ophthalmia (SO) in a one-eyed patient who was successfully managed with systemic immunosuppression therapy. A 77-year-old one-eyed female presented with progressive diminution of vision in the left eye (OS) for one month. She had previously undergone a right eye (OD) pars plana vitrectomy elsewhere for exogenous post-operative endophthalmitis (after manual small incision cataract surgery five months ago), following which she developed phthisis. Granulomatous panuveitis and advanced cataract were noted in the OS. Findings on multimodal imaging, including spectral domain optical coherence tomography (SD-OCT), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and B-scan ultrasonography, were consistent with those of chronic SO. Promptly, oral steroids and systemic immunosuppressants were initiated under the supervision of a rheumatologist. At the three-week follow-up, complete resolution of clinical signs was observed on multimodal imaging. Chronic SO may present with ambiguous clinical signs, leading to a diagnostic dilemma. This may cause a delay in initiating treatment, which can prove to be highly detrimental, especially in one-eyed patients. Multimodal imaging is critical in excluding differential diagnoses and proves to be indispensable in the timely management of this sight-threatening condition.