Summary We describe a case of culture-negative infective endocarditis due to Neisseria gonorrhoeae, where the application of metagenomics shotgun sequencing in blood played a pivotal role in elucidating the underlying aetiology, guiding targeted therapy and ultimately resulting in the patient’s complete recovery. Beyond its immediate clinical impact, prompt treatment bears significant implications for public health. The utilisation of molecular testing emerges as a valuable strategy to enhance diagnostic accuracy, particularly in cases involving fastidious organisms that are infrequently associated with infective endocarditis.