Purpose <p>The aim of the present systematic review is to assess the effectiveness of nuclear medicine methods to improve the diagnostic accuracy of stereotactic brain biopsies (SBB).</p> Methods <p>A search in Medline, Cochrane, and Scopus databases until 22^nd August 2024 was performed to retrieve relevant studies, aided by a manual search in Google Scholar. After applying predetermined inclusion and exclusion criteria, a data extraction was performed. The risk of bias and concerns regarding applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool.</p> Results <p>Thirteen studies (9 prospective and 4 retrospective) with a total of 337 patients were included in this systematic review. There was a high risk of bias at least in one domain in all studies, while in 4 studies there were high concerns regarding applicability at least in one domain. Positron emission tomography (PET) was used in 12 studies and single photon emission computed tomography (SPECT) in 1 study to design the trajectories of the biopsies. A diagnosis was established through SBB in 282 out of 291 patients, while for the remaining 46 patients there was no relevant data in the studies. Two studies provided data on sensitivity (76 - 81.2 %), specificity (50 - 80 %), and Area Under the Curve (AUC) (56.2 - 89 %).</p> Conclusion <p>Nuclear medicine has the potential to increase the diagnostic accuracy of SBB by improving targeting precision. Among the radiotracers, ¹¹C-methionine emerged as the most effective, providing superior visualization of the metabolic active region of a brain tumor.</p>