Background <p>Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) represent life-threatening mucocutaneous reactions, predominantly triggered by medications. This case report presents a rare instance of SJS-TEN overlap in a young Indian female precipitated by the combined use of fluoroquinolone (ofloxacin), cephalosporin (cefixime), and paracetamol—an uncommon drug triad not widely reported in existing literature. The case highlights the importance of early diagnosis, thorough drug history evaluation, and the challenges of managing polypharmacy-induced severe cutaneous adverse reactions (SCARs).</p> Case presentation <p>A 29-year-old Indian female developed widespread dusky purpuric plaques, mucosal erosions (oral, genital, conjunctival, nasal), and bullae six days after local consultation with ofloxacin, cefixime, paracetamol, and other symptomatic agents. She presented to the emergency department with painful vesiculobullous eruptions involving &gt; 10% body surface area, mucosal ulcerations, eye involvement with crusting, and systemic symptoms including fever, vomiting, and urinary discomfort. Laboratory investigations revealed anemia, elevated RDW, and positive ketones in urine. Diagnosis of SJS-TEN overlap was made clinically. The patient was managed with a multi-disciplinary approach involving systemic corticosteroids (IV dexamethasone), hydration, antibiotics (azithromycin), antihistamines, electrolyte balance, topical agents, ophthalmic care, and pain management. The extensive yet individualized treatment regimen reflected a robust pharmacovigilance response to avoid further drug-induced complications. Improvement was noted with complete re-epithelialization and symptomatic resolution over two weeks.</p> Conclusion <p>This case highlights the necessity for clinicians to maintain high suspicion for SCARs in patients presenting with mucocutaneous symptoms and recent drug exposure—even with commonly used medications not frequently associated with SJS-TEN. The unique presentation involving synchronous ocular, nasal, oral, and genital erosions alongside use of a rare drug combination strengthens the need for early recognition, comprehensive clinical assessment, and cautious prescription practices. Individualized treatment and close monitoring are crucial in preventing mortality and minimizing complications. This case underscores the importance of pharmacovigilance and personalized care in managing drug-induced hypersensitivity reactions, especially in resource-limited or polypharmacy scenarios.</p>