Aim and Background. The purpose of this systematic review and meta-analysis was to evaluate the difference in wear resistance between CAD Zirconia reinforced lithium silicate and CAD Lithium disilicate glass ceramics. Different CAD/CAM ceramic materials for prosthetic rehabilitation are manufactured but which material has better wear resistance for durable outcomes needs to be evaluated. Methods. Two independent reviewers searched the MEDLINE/ PubMed, and EBSCO databases and the Google Scholar search engine for in-vitro studies published from January 2010 to March 2023 to identify relevant studies evaluating the wear resistance between CAD Zirconia reinforced lithium silicate and CAD Lithium disilicate glass ceramics. Meta-analysis was performed to evaluate the quantitative data on the amount of volume loss to measure the wear properties of both materials. Results. A total of 364 titles were obtained by electronic database search, of which 27 were duplicates. A total of 337 abstracts were screened, and 274 not relevant to the topic were excluded. Forty-two articles were eligible for full-text assessment. After the screening of full-text articles as per the selection criteria, 30 studies were excluded (18 studies with inappropriate outcomes measured, 6 studies done on monolithic zirconia, and 6 studies measured surface roughness). For qualitative synthesis, 12 studies were included. For the meta-analysis, 12 studies were included. A statistically significant difference in wear resistance was observed between the CAD Zirconia reinforced lithium silicate and CAD Lithium disilicate glass ceramics (P=.01, pooled mean difference=-0.03[-0.05,-0.01], CI=95%). Conclusions. CAD Zirconia reinforced lithium silicate showed statistically higher wear resistance than compared with CAD Lithium disilicate glass ceramics. Clinical Significance. For anterior and posterior fixed dental prosthesis clinicians can opt for CAD Zirconia- reinforced lithium silicate as an esthetically durable prosthetic material.