<p>This report describes the case of a 28-year-old woman, who presented with a two-week history of severe ocular pain and photophobia in her right eye. She was a soft contact lens wearer with no history of ocular trauma or systemic illness. Ophthalmic examination revealed conjunctival hyperemia, epithelial irregularities, and a developing ring-shaped stromal infiltrate. In vivo confocal microscopy demonstrated double-walled hyperreflective cysts, and culture followed by PCR and sequencing confirmed the presence of <i>Acanthamoeba</i> T4 genotype. Despite intensive treatment with topical polyhexamethylene biguanide, chlorhexidine, propamidine, and voriconazole, as well as oral miltefosine, the infection progressed, leading to stromal necrosis. The patient underwent two therapeutic penetrating keratoplasties; however, the disease continued to advance, eventually resulting in phthisis bulbi and permanent vision loss. This case highlights the potential for aggressive, clinically refractory <i>Acanthamoeba</i> keratitis caused by the T4 genotype, emphasizing the importance of early diagnosis, vigilant monitoring, and timely surgical intervention in resistant cases.</p>