BACKGROUND: Cabazitaxel (CAB) has been approved for the treatment of patients with progressed metastatic castration-resistant prostate cancer (mCRPC) after receiving docetaxel. To assess the efficacy and safety of CAB in mCRPC patients through systematic review and network meta-analysis. METHODS: Randomized controlled studies on the treatment of mCRPC with CAB in PUBMED, EMBASE, Cochrane, and Web of Science were searched. Relevant studies that met pre-set criteria were determined, and the quality of included studies was evaluated using the National Institutes of Health-Quality Assessment Tool. After the data was extracted, data analysis was conducted in R 4.3.2. Overall survival (OS), progression-free survival (PFS), and serious adverse events (SAEs) were used as the primary outcomes, and HR (hazard ratio) or RR (risk ratio) and their 95% confidence intervals (95% CrI) were calculated as effect sizes. RESULTS: A total of 13 studies were included, involving 5,814 patients. The overall risk of bias for 13 studies was low. The results showed that CAB 25 mg/m significantly improved OS compared to androgen receptor pathway inhibitor (ARPI) (1.50 [1.30, 1.70]) and MIT (1.40 [1.20, 1.70]), but its efficacy was inferior to Lu-PSMA (0.42 [0.27, 0.67]) and therapeutic drug monitoring (TDM)-CAB (0.51 [0.38, 0.70]). CAB 25 mg/m could significantly improve PFS compared to CAB + CP (1.40 [1.10, 2.00]), ARPI (1.80 [1.50, 2.30], MIT (1.40 [1.20, 1.60]), but its efficacy was not as good as CAB 20 mg/m (0.92 [0.82, 1.00]), Lu-PSMA (0.58 [0.41, 0.80]), TDM-CAB (0.67 [0.51, 0.86]). In addition, compared to CAB 25 mg/m, CAB + CP may significantly increase the risk of SAEs (3.10 [1.70, 5.90]). CONCLUSION: CAB is an effective treatment in mCRPC, and combining it with other treatment methods may enhance efficacy, but attention should be paid to the occurrence of adverse events.