PurposeThis meta-analysis aimed to determine how spiritual interventions affect cancer patients’ physical, emotional, and spiritual outcomes and quality of life. MethodsBetween 2012 and May 2024, the Cochrane Library, Scopus, PubMed, and Web of Science were searched considering the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Twenty-six randomized controlled trials were included, and 16 were synthesized in the meta-analysis. Bias risk was evaluated using the Cochrane risk-of-bias methodology for randomized studies. The Grading of Recommendations, Assessment, Development, and Evaluations tool was employed for evidence certainty. Heterogeneity was expressed through I2 and Q statistics. Hedge's g was calculated for effect sizes. Egger's and Kendall's Tau were used for publication bias. ResultsSpiritual interventions yielded beneficial effects on fatigue (Hedges's g = 0.900, p < 0.001) and pain (Hedges's g = 0.670, p < 0.001) but not for overall symptom burden (Hedges's g = 0.208, p = 0.176). Significant effects were found for anxiety (Hedges's g = 0.301, p < 0.001), depression (Hedges's g = 0.175, p = 0.016), and psychological distress (Hedges's g = 0.178, p = 0.024), except for hopelessness (Hedges's g = 0.144, p = 0.091). Spiritual interventions enhanced faith (Hedges's g = 0.232, p = 0.035), the meaning of life (Hedges's g = 0.259, p = 0.002), spiritual well-being (Hedges's g = 0.268, p < 0.001), and quality of life (Hedges's g = 245, p < 0.001). Moderator analysis pointed out that cancer stage, total duration, delivery format, providers' qualification, content, and conceptual base of spiritual interventions significantly affect physical, emotional, and spiritual outcomes and quality of life. ConclusionThis meta-analysis highlighted the benefits of spiritual interventions with varying effect sizes on patients’ outcomes, as well as quality of life in cancer, and shed on how to incorporate these approaches into clinical practice.