--- - |2+ Abstract Objectives To synthesize the evidence of existential interventions in adult patients with cancer. Methods Embase, MEDLINE, CENTRAL, CINAHL, PsycINFO, PSYNDEX, and the WHO ICTRP were searched up until 26 January 2018. Eligibility criteria for studies were (1) adult patients with cancer, (2) evaluation of existential interventions, (3) compared with active/non‐active control, (4) assessing relevant spiritual, psychological, or physical outcomes, and (5) conducted as randomized controlled trials. Standardized mean differences (Hedges' g) were calculated, and meta‐analyses were conducted using random effects models. Effects were aggregated within four time horizons (post‐treatment; ≤3 months; ≤6 months; >6 months). Heterogeneity was assessed by forest plots and I2. Risk of bias was assessed using the Cochrane Risk of Bias Tool. This review has been registered with Prospero (CRD42016042895). Results A total of 3461 records were identified, of which 30 unique studies (3511 participants) were included in the review and 24 studies were included in meta‐analyses. Existential interventions showed significant effects on existential well‐being (g = 0.52; CI[0.13; 0.91; k = 10; I2 = 85%) and quality of life (g = 0.21; CI[0.01; 0.42]; k = 17; I2 = 75%) at post‐treatment, on hope at post‐treatment (g = 0.43; CI[0.12; 0.74]; k = 12; I2 = 86%) and after 6 months (g = 0.25; CI[0.02; 0.48]; k = 3; I2 = 0%) and on self‐efficacy at post‐treatment (g = 0.50; CI[0.09; 0.90]; k = 2; I2 = 0%). No significant effects were found on the remaining outcomes and time points. Significant moderator effects were found for professional background of therapists, intervention concept, number of sessions, and setting. Conclusions This systematic review and meta‐analysis provides evidence that adult patients with cancer across all stages and types benefit from existential interventions. Future research should strive towards a higher standardization in particular with respect to outcome assessments. - Psycho-Oncology, EarlyView.