Prurigo nodularis (PN) is a chronic inflammatory skin disorder characterized by intensely pruritic nodules. The pathogenesis of PN involves immune dysregulation, with a predominance of T helper (Th2)-type inflammation, including interleukin (IL)-4, IL-5, IL-13, and IL-31. Nemolizumab, an IL-31 receptor A inhibitor, was newly approved for PN in 2024. We report a case of erythema multiforme (EM) that developed three weeks after the first administration of nemolizumab. Three weeks post-injection, she developed multiple targetoid edematous erythematous patches and plaques on her trunk and limbs, leading to a clinical diagnosis of EM. Since she had no new medications and no recent history of infections, we inferred that the development of EM was likely associated with the administration of nemolizumab. The pathophysiology of EM involves a predominant Th1-driven inflammatory response. Therefore, nemolizumab likely suppressed Th2 inflammation, leading to compensatory Th1 hyperactivation, which may have triggered EM. To our knowledge, this may be the first reported case of EM following nemolizumab treatment for PN. Further research is necessary to investigate its immunomodulatory effects and potential adverse events.