Prostate cancer (PCa) has high prevalence rates in men and is a leading cause of cancer-related death. Transrectal (TR) biopsy has traditionally been the gold standard for diagnosis, but transperineal (TP) biopsy is increasingly favoured due to its lower infection risk. However, debate remains regarding which method has superior cancer detection rates. This review compares the efficacy and safety of the TP as compared to the TR prostate biopsy approach, summarizing the largest body of evidence available to date. A literature search was performed on the PubMed, Google Scholar, Cochrane Library, and Embase databases. We searched from the inception of the databases up to August 2024 for relevant studies comparing the cancer detection rate of TP versus TR prostate biopsy and compared their complication rates. Twenty-one studies met the inclusion criteria. The pooled odds ratios with 95% confidence intervals were calculated to evaluate the differences between the TR and TP groups in the PCa detection rate. This meta-analysis included 21 studies (6 randomized control trials and 15 cohort studies) with a total of 13,818 patients (TP = 7917; TR = 5901), who were accrued between 2008 and 2024 and divided into the TR group and the TP group. The analysis revealed no significant difference in prostate cancer detection rates between the TP and TR approaches in both RCTs (OR 1.02, 95% CI (0.74, 1.41), p = 0.90) and cohort studies (OR 1.07, 95% CI (0.85, 1.35), p = 0.36). Complication profiles were largely comparable; TP demonstrated a significantly lower risk of urinary tract infections (OR 0.26, 95% CI (0.11, 0.61)) but no notable differences in acute urinary retention, haematuria, or rectal bleeding. Our findings advocate the TP approach as a safer biopsy alternative where feasible, particularly in infection-sensitive populations, without compromising diagnostic accuracy. MRI should complement biopsy strategies to enhance diagnostic precision. Future research should focus on standardized, large-scale RCTs to further refine and personalize prostate cancer diagnostic pathways.