Severe cutaneous adverse reactions (SCARs) to drugs are associated with morbidity, mortality, healthcare costs, and challenges in drug development. It is important to identify the SCAR type early by using strict diagnostic criteria because they may require different treatments, follow-ups, and short- or long-term prognoses. A 68-year-old woman admitted to our hospital presented with fever and rashes for 10 days. This case exhibited many features that suggested acute generalized exanthematous pustulosis (AGEP). However, the course of treatment and verified clinical features led to a diagnosis of AGEP and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome that was induced by carbamazepine and levofloxacin after a herpes zoster infection. AGEP combined with DRESS syndrome is a complicated and rare drug-induced dermatological eruption that follows a course similar to DRESS syndrome and more recalcitrant than the course seen with typical AGEP. The associated factors for the SCARs in our patient included age, history of allergy, viral infection, and drugs interacting with specific HLA loci. Improving our understanding of these factors can improve the treatment and prevention of SCARs in these patients.