Background: Prostate cancer consists the second most commonly diagnosed malignancy in men and a global threatening health condition with severe following outcomes. Screening via the digital rectal examination (DRE), prostate-specific antigen (PSA) test, or both is widely used in clinical practice and supported as early detection tools. Although neither of the two tests, PSA and DRE, are appropriate to be used alone for screening of prostate cancer. This meta-analysis aims to find out the role of these techniques used in conjunction in a primary healthcare setting to diagnose prostate cancer(PC).Methods: This meta-analysis was conducted according to (PRISMA) guideline. A comprehensive literature search was performed to PubMed, Cochrane, and Google Scholar from November 2022 to April 2023. Diagnostic studies were retrieved with no restrictions on publication date, country, patient's age or clinical setting. The selection of studies proceeded based on specific inclusion and exclusion criteria without restrictions to particular study designs, language or publication dates and followed by data extraction and statistical analysis. The gold standard reference in the included studies was biopsy for prostate carcinoma.Results: Twelve studies with 175379 patients who underwent DRE Vs Biopsy and fifteen studies with 22006 patients who measured PSA cutoff 4 ng/ml VS biopsy were included in our meta-analysis. Overall, the overall sensitivity, specificity, and PPV of DRE was 57.8% (95% CI 52 -63.6 %), 44.7% (95% CI 37.6 - 51.7%), and 29.8% (95% CI 24.1 - 35.5%) respectively. The diagnostic accuracy of DRE was 48.5% with a Younden index of 2.5%. Also, the sensitivity, specificity, and PPV for PSA cutoff level of more than 4 ng/mL were found to be 57.7 % (95% CI 51.2 - 64.2%) ,82.3% (95% CI 79.7 - 85%), and 67.6% (95% CI 62.7 - 72.6%) respectively. In addition, the diagnostic accuracy of the PSA cutoff level of more than 4 ng/mL was 72.7% with a Younden index of 0.4. Conclusion: The use of DRE and PSA has high diagnostic accuracy in PC, although the lone application of each one is not statistically strong and diagnostically accurate. Their contribution could form an optimistic clue in future updates considering this condition.