Despite successful fusion rates with iliac crest bone graft (ICBG), donor-site morbidity and increased operating time remain a considerable limitation and drive the search for alternatives. In this systematic review, grafts with additional cellular supplementation were compared with ICBG for spinal arthrodesis. We compared safety, efficacy and long-term outcomes, thus providing the current and relevant evidence for orthopaedic surgeons to make informed choices regarding this rapidly developing field. An electronic literature search was conducted according to the PRISMA guidelines by two independent reviewers for articles published up to 1st March 2023 using PubMed, EMBASE and the Cochrane Central Register of Controlled Trial. Cellular allografts were not included. The following data were extracted: Number of patients, type of graft, fusion assessment method, follow-up duration, fusion rates, clinical outcomes and complications. The methodological quality of evidence (MQOE) was assessed using the Risk of Bias 2 (RoB-2) tool and Risk of Bias In Non-Randomised Studies (ROBINS) tool developed by Cochrane for evaluating bias in randomised and non-randomised studies. Ten studies fulfiled the inclusion criteria, including 465 patients. The mean number of patients per study was 43.8 (std dev. 28.81, range 12-100). Two studies demonstrated cell-based therapy to be significantly more successful in terms of fusion rates compared to ICBG. However, the remaining eight demonstrated equivocal results. No study found that cell-based therapy was inferior. No difference was seen between the two groups in three studies who focused on degenerative cohorts. No difference in functional outcome scores was seen between the groups. A number of different preparation techniques for cell-based grafts were used throughout the studies. Cell-based therapy offers a promising alternative to ICBG in spinal fusion surgery, which could help reduce the associated morbidity to patients. This review found that cell-based therapy is non-inferior to iliac crest bone graft and may offer patients an alternative treatment option with fewer complications and reduced post-operative pain. However, the literature to date is limited by heterogeneity of the cell preparation and grafting process. Future research with a unified approach to the cell preparation process is required to fully delineate the potential advantages of this technology.