Background: This study examines the clinical efficacy of daratumumab when combined with other therapeutic agents in patients with multiple myeloma, with a focus on key outcomes including overall response, progression-free survival (PFS), and stringent complete response (sCR). Methods: A systematic literature search was conducted using PubMed, Web of Science, Scopus, and the Cochrane Library. Statistical analyses were performed with R software (version 4.2.2). Between-study heterogeneity was assessed using the Cochrane Q test and the I² statistic, while potential publication bias was evaluated through Egger’s regression test and visual inspection of funnel plots. Results: The meta-analysis revealed that daratumumab-containing regimens were associated with a 54.4% reduction in the risk of disease progression or death (hazard ratio[HR] 0.4558; 95% confidence-interval [CI]: 0.4031–0.5154). Similar results were observed using a random-effects model (HR 0.4667; 95% CI: 0.3771–0.5776), despite moderate heterogeneity (I² = 66.7%). Moreover, patients treated with daratumumab were approximately 2.4 times more likely to achieve a stringent complete response (odds-ratio[OR] 2.38; 95% CI: 1.80–3.15), with moderate heterogeneity across studies (I² = 58.2%). Conclusions: Incorporating daratumumab into standard therapy for multiple myeloma significantly enhances progression-free survival and the rate of stringent complete response. Despite some heterogeneity, the consistent positive outcomes support its use as an effective treatment option in clinical practice.