Mycobacterium franklinii (Mfra) is a recently identified member of the Mycobacterium chelonae-abscessus complex (MCAC), a rapidly growing, acid-fast bacilli that have the potential to cause invasive human infections. Identification of Mfra is crucial for selecting the appropriate antimicrobial therapy, as Mfra displays a unique susceptibility profile compared to other MCAC members. The literature on Mfra is limited, with a few studies focusing on respiratory and skin infections. To our knowledge, we describe the first reported case of cardiac involvement associated with Mfra bacteremia in a patient with acute lymphoblastic leukemia. The isolation of Mfra through a next-generation sequencing test allowed for prompt identification and subsequent implementation of tailored antimicrobial agents, ultimately resulting in positive clinical outcomes. This case also emphasizes the significance of next-generation testing in managing immunocompromised patients with persistent fever.