Nocardiosis, is a potentially life-threatening disease, especially in immunocompromised individuals where it manifests as a disseminated disease. Infective Endocarditis (IE) is a rare disease with significant morbidity and mortality. Importantly, even though there are scarce data of IE by Nocardia spp. in the literature, a review adequately summarizing systematically all available evidence on the topic is lacking. The aim of this study was to systematically review all cases of IE by Nocardia spp. and describe the epidemiology, microbiology, clinical characteristics, treatment and outcomes of this infection. A systematic review of PubMed, Scopus and Cochrane library (through 7 December 2021) for studies providing epidemiological, clinical, microbiological as well as treatment data and outcomes of patients with IE by Nocardia spp. was performed. A total of 25 studies providing data for 26 patients were included. A prosthetic valve was present in 30.8%, while the most common microorganism was N. asteroides. Aortic valve was the most commonly infected intracardiac site, followed by the mitral valve. Diagnosis was most commonly performed with transthoracic echocardiography, while the diagnosis was made at autopsy in 11.5%. Co-trimoxazole, aminoglycosides and carbapenems were the most commonly used antimicrobials. Clinical cure was noted in 73.1%, while mortality was 26.9%. This systematic review thoroughly describes IE by Nocardia and provides information on epidemiology, clinical presentation, treatment and outcomes.