Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is an erythematous, photodistributed, scaly, and annular cutaneous eruption that is clinically similar to subacute cutaneous lupus erythematosus. However, DI-SCLE is associated with medication use and generally resolves or greatly improves following discontinuation. Chemotherapeutic agents are common triggers of DI-SCLE. We report a patient with breast cancer who experienced multiple episodes of DI-SCLE associated with the use of different chemotherapeutic agents for treatment-resistant cancer. Notably, to the best of our knowledge, this case highlights the first reported association of DI-SCLE with trastuzumab deruxtecan. Additionally, this case is unique owing to a component of radiation recall dermatitis, as the rash was prominent in areas that had prior ionizing radiation. A prior history of DI-SCLE in oncology patients who continue to undergo treatment should prompt clinicians to consider DI-SCLE when faced with a new photodistributed, erythematous, annular, and scaly eruption. Early initiation of immunomodulating agents like hydroxychloroquine in patients with a history of moderate to severe DI-SCLE to chemotherapy who continue to undergo anti-cancer treatment may provide benefit and warrants further investigation.