Background: Several treatment options are available for relapsed refractory multiple myeloma(RRMM). However, in the absence of direct-comparative trials, it is unclear how to choose optimal therapy in RRMM. We conducted a network meta-analysis (NMA) to assess the comparative efficacy of different treatment options in RRMM. Methods: Standard electronic databases were searched for abstract and full-text publications of phase 2/3 randomized controlled trials (RCTs) assessing treatment regimens in RRMM. Progression free survival (PFS) , overall survival (OS), complete response (CR), and very good partial response (VGPR) were analyzed. Mixed treatment comparisons were made using fixed-effect network meta-analysis (NMA) within the frequentist framework due to sparse direct evidence. Sensitivity analyses were conducted using the Bayesian approach. Publication bias was assessed by visual inspection of comparison-adjusted funnel plots. P-score plots were used to assess relative rankings of the treatments. R statistical software v 4.0.3 was used to conduct the analyses. Results: After a review of 1137 citations, A total of 37 relevant studies were included in systematic review and 30 studies were analyzed in the network meta-analysis (29 contributed for PFS; 18 for OS; 23 for CR; 25 for VGPR). Mixed treatment comparisons showed high likelihood of PFS benefit with triplet regimens; Isatuximab-Carfilzomib-Dexamethasone (Isa-Kd; P-score: 0.98), followed by Daratumumab-Carfilzomib-Dexamethasone (DKd; P-score: 0.93), Daratumumab-Bortezomib-Dexamethasone (DVd P-score: 0.92), Elotuzumab-Pomalidomide-Dexamethasone (EPd); P-score: 0.84), and Isatuximab-Pomalidomide-Dexamethasone (Isa-Pd; P-score: 0.80) when compared to monotherapy and different doublet regimens. Isa-Kd and DKd continued to show significant PFS advantage when compared to Kd doublet. High likelihood of OS benefit was observed with Carfilzomib-Lenalidomide-Dexamethasone (KRd); P-score: 0.86) followed by Kd (P-score: 0.83), and DVd (P-score: 0.82). However, trials did not consistently report data for OS and most of the mixed treatment comparisons were statistically insignificant. Similar results were observed for CR and VGPR with triplet regimens showing better likelihood for achieving CR and VGPR. Conclusions: This NMA provide most updated evidence on different treatment options in RRMM and can serve as a contemporary guidance in the absence of head-to-head trials. The weight of current evidence favors the use of triplet regimens. Isa-Kd, DKd, DVd, EPd and Isa-Pd showed no statistically significant difference in terms of PFS in RRMM.