Background: Acromial and scapular spine fractures after reverse total shoulder arthroplasty (RTSA) can be devastating complications leading to substantial functional impairments. The purpose of this study was to review factors associated with increased acromial and scapular spine strain after RTSA from a biomechanical standpoint. Methods: A systematic review of the literature was conducted based on PRISMA guidelines. PubMed, Embase, OVID Medline, and CENTRAL databases were searched and strict inclusion and exclusion criteria were applied. Each article was assessed using the modified Downs and Black checklist to appraise the quality of included studies. Study selection, extraction of data, and assessment of methodological quality were carried out independently by two of the authors. Only biomechanical studies were considered. Results: Six biomechanical studies evaluated factors associated with increased acromial and scapular spine strain and stress. Significant increases in acromial and scapular spine strain were found with increasing lateralization of the glenosphere in four of the included studies. In two studies, glenosphere inferiorization consistently reduced acromial strain. The results concerning humeral lateralization were variable between four studies. Humeral component neck-shaft angle had no significant effect on acromial strain as analysed in one study. One study showed that scapular spine strain was significantly increased with a more posteriorly oriented acromion (55° vs. 43°; p < 0.001). Another study showed that the transection of the coracoacromial ligament increased scapular spine strain in all abduction angles (p < 0.05). Conclusions: Glenoid lateralization was consistently associated with increased acromial and scapular spine strain, whereas inferiorization of the glenosphere reduced strain in the biomechanical studies analysed in this systematic review. Humeral-sided lateralization may increase or decrease acromial or scapular spine strain. Independent of different design parameters, the transection of the coracoacromial ligament resulted in significantly increased strains and scapular spine strains were also increased when the acromion was more posteriorly oriented. The results found in this systematic review of biomechanical in-silico and in-vitro studies may help in the surgical planning of RTSA to mitigate complications associated with acromion and scapular spine fracture.