This study aimed to systematically compare the patients undergoing lateral MSFA therapies utilizing bovine-originated xenografts versus varied synthetic bone grafting materials. Pubmed, Scopus, Embase, and Cochrane Library were searched up to April 2023, compensated by a manual search in selected journals. Studies reporting histological outcomes (residual bone graft, newly formed bone, non-mineralized tissue) and clinical outcomes (implant survival, ISQ value) were included. Several analyses were performed, including meta-analysis, sensitivity study, and Egger's regression tests. Sixteen clinical/randomized control trials were included in this systematic review, among which 12 were enrolled in a meta-analysis. The percentage of newly formed bone within the grafted sinuses by hybrid HA/TCP was significantly higher than those by xenografts (WMD 2.85, 95%CI [0.72; 4.99]), but those grafted by pure HA (WMD -1.72, 95%CI [-3.15; -0.29]) or TCP (WMD -7.10, 95%CI [-13.02; -1.17]) were significantly lower than xenograft counterparts. The residual bone graft and non-mineralized tissue yielded by synthetic HA, TCP, and HA/TCP showed no significant differences with the xenograft group. The chemistry of grafted bone substitutes in lateral MSFA influenced the quantity of newly formed bone. Those grafted with hybrid HA/TCP yielded the highest amount of new bone compared to bovine-originated HA. However, this influence was not significant on residual bone graft and non-mineralizedtissue.