Herein, we present a case report that describes the first documented use of T-DXd in a perioperative regimen for a patient with HER2 exon 20 insertion-containing lung adenocarcinoma, which provides preliminary clinical evidence supporting the potential of T-DXd as a neoadjuvant and adjuvant therapy, where it provided notable tumor regression before surgery and contributed to durable postoperative remission. The gene discussed is ERBB2; the disease is neoplasm.