Tuberculosis (TB) is a global health problem, in which the majority of cases occur in population-dense developing countries. Despite advances in various diagnostic TB modalities, extrapulmonary TB remains a challenge due to complexities related to its diagnostic approach. Hereby, we present a rare case of endocarditis and spondylodiscitis associated with Mycobacterium tuberculosis (MTB). This case report highlighted the challenges faced in diagnosing blood culture-negative infective endocarditis (BCNIE). We also emphasized the importance of considering MTB as etiology of BCNIE, particularly in endemic TB areas.