This case concerns an 83-year-old woman hospitalized after two emergency department visits due to generalized weakness and poor appetite that continued to worsen over one month. Through comprehensive geriatric assessment, our geriatric team found that the patient had multiple geriatric syndromes and conditions, including cognitive abnormalities, depressive symptoms, decreased physical function, pain, and malnutrition. These atypical presentations finally led to the diagnosis of infective endocarditis. In addition to improving diagnostic accuracy, implementing comprehensive geriatric assessment helps reduce the risk of the surgery and post-operative complications and deconditioning, thereby improving the patient’s quality of life after surgery.