BACKGROUND: The increasing incidence of primary total knee arthroplasty (TKA) has led to an increase in both the incidence and the cost burden of revision TKA procedures. This study aimed to review the literature on the cost of revision TKA for septic and aseptic causes and to identify the major cost components contributing to the cost burden. METHODS: We searched MEDLINE (OvidSp), Embase, Web of Science, Cochrane Library, EconLit, and Google Scholar to identify relevant studies. Selection, data extraction and assessment of the risk of bias and cost transparency within the studies were conducted by two independent reviewers, after which the cost data were analysed narratively for 1- or 2-stage septic revision without re-revision; 2-stage septic revision with re-revision; and aseptic revision with and without re-revision, respectively. The major cost components identified in the respective studies were also reported. RESULTS: The direct medical cost from the healthcare provider perspective for high-income countries for 2-stage septic revision with re-revision ranged from US$66,629 to US$81,938, which can be about 2.5 times the cost of 1- or 2-stage septic revision without re-revision, (range: US$24,027 - US$38,109), which can be about double the cost of aseptic revision without re-revision (range: US$13,910 - US$29,213). The major cost components were the perioperative cost (33%), prosthesis cost (28%), and hospital ward stay cost (22%). CONCLUSIONS: Septic TKA revision with re-revision for periprosthetic joint infection (PJI) increases the cost burden of revision TKA by 4 times when compared to aseptic single-stage revision and by 2.5 times when compared to septic TKA revision that does not undergo re-revision. Cost reductions can be achieved by reducing the number of primary TKA that develop PJI, avoidance of re-revisions for PJI, and reduction in the length of stay after revision. TRIAL REGISTRATION: PROSPERO; CRD42020171988 .