Objective This study aims to summarize the clinical characteristics of patients with scrub typhus in atypical epidemic areas, and explore the application value of metagenomic next-generation sequencing (mNGS) and targeted next-generation sequencing (tNGS) in etiological diagnosis. Methods A retrospective analysis was conducted on the clinical data of seven patients with scrub typhus diagnosed by next-generation sequencing (NGS) at Ji'an Central People's Hospital from May 2025 to January 2026. Among them, three patients with respiratory symptoms or lung infection as the main manifestation underwent tNGS testing, while four patients with sepsis or systemic infection as the main manifestation underwent mNGS testing. Data on the patients' clinical manifestations, laboratory tests, NGS results, diagnosis time, and treatment outcomes were collected. Results Among the seven patients, four were male and three were female, with a median age of 69 years. All patients presented with high fever as the initial symptom, and only one patient exhibited typical eschar. All seven patients had elevated C-reactive protein levels, five of whom also had thrombocytopenia, and all seven had abnormal liver function. NGS detected Orientia tsutsugamushi sequences within 24 to 72 hours after sample submission. The duration from patient admission to obtaining etiological results ranged from 2 to 4 days, with a median of 3 days. After treatment with doxycycline or minocycline adjusted based on NGS results, the patients' temperatures returned to normal within 1 to 3 days, with a median fever reduction time of 2 days. All patients were cured and discharged. Conclusions Patients with scrub typhus in atypical epidemic areas often exhibit nonspecific clinical manifestations, making them prone to misdiagnosis and missed diagnoses. For high-risk febrile patients who fail to respond to empirical anti-infective treatment and have unidentified causes, NGS can serve as an important supplementary diagnostic tool. Timely NGS testing can facilitate rapid and precise identification of pathogens, providing crucial evidence for subsequent adjustments to targeted anti-infective regimens.