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Purpose: To report a challenging case of corneal descemetocele following Nd:YAG laser capsulotomy for posterior capsule opacification in a patient with Steven Johnson syndrome (SJS). Observations: A single-eye 52 year-old man, with a history of Steven Johnson syndrome, presented with severe eye pain and profound vision reduction in his left eye two days after undergoing Nd:YAG laser capsulotomy using the standard Abraham contact lens. A corneal descemetocele was identified and subsequently confirmed by anterior segment optical coherence tomography. He was promptly treated with the application of a therapeutic contact lens and sustained antibiotic regimen (preservative-free fluoroquinolone drops every 4 hours for 6 weeks) until healing of the corneal epithelium. Throughout the following eight weeks AS-OCT showed favorable anatomical and functional outcomes, achieving a substantial spontaneous healing. Conclusions and Importance: Corneal descemetocele may occur after Nd:YAG laser capsulotomy in patients with Steven Johnson syndrome. This case strengthens the critical importance of a careful preoperative assessment and meticulous postoperative management in high-risk patients, such as those with Steven Johnson syndrome, even after seemingly routine and safe ophthalmic procedures.