Abstract Background Several nuclear imaging methods may predict postoperative liver function and outcome, but none has achieved recommendations in clinical guidelines. The purpose of this systematic review was to summarize the existing knowledge on this topic. Methods MEDLINE and Web of Science were searched for studies investigating nuclear medicine imaging methods for the prediction of postoperative liver function in patients undergoing localized, liver-directed treatments. The postoperative endpoints were clinical outcome (morbidity and mortality) as well as measures of postoperative liver function, e.g., liver function assessed by biochemical tests or nuclear imaging. Results A total of 1352 references were identified, of which 82 fulfilled the eligibility criteria and were included in the review. Most studies (n = 63) were retrospective studies. The vast majority of studies assessed [^99mTc]Tc-galactosyl serum albumin (GSA) (n = 57) and [^99mTc]Tc-mebrofenin (n = 19). Liver resection was entirely or partly major (involved at least three segments) in 78 reports. There were notable variations in the research methodology, e.g., image acquisition, imaging variables, and endpoints. Thirty-seven studies reported on postoperative mortality, of which most reported descriptive data at the patient level. Of the four reports that performed multivariate analyses, two showed significant predictive results of isotope-based preoperative tests. Fifty-two papers presented data on postoperative liver failure. Multivariate predictive analyses were performed in eighteen trials, of which fifteen showed the significant value of nuclear medicine tests. Conclusion There is sparse evidence supporting the significant value of nuclear medicine imaging methods in predicting postoperative mortality. In contrast, a notable number of trials showed a significant prediction of liver failure in multivariate analyses. The research methodology was heterogeneous and exploratory in most trials. Documentation of nuclear medicine tests in this setting awaits the results of properly designed, prospective trials with the standardization of both the nuclear medicine test and endpoints.