PURPOSE: This study aimed to investigate whether socio-demographic, clinical, and intervention-related variables moderate the effects of exercise on depression and anxiety symptoms in cancer survivors. METHODS: Data from 26 RCTs in the POLARIS database were analyzed using a one-step individual participant data (IPD) meta-analytic approach with linear mixed models to assess exercise effects on depression and anxiety symptoms (z-scores). Interaction terms were added to these models to explore moderators. Results are presented as betas (corresponding to Cohen's d effect size). RESULTS: Albeit statistically significant, exercise demonstrated negligible effects on symptoms of depression (β = - 0.11; 95% CI = - 0.16; - 0.06) and anxiety (β = - 0.07; 95% CI = - 0.12; - 0.02) compared to controls. The effects of exercise interventions on depressive symptoms were larger for patients who were not living with a partner (β = - 0.23; 95% CI = - 0.35; - 0.11), had a low/medium education level (β = - 0.14; 95% CI = - 0.21; - 0.07), and who had moderate-to-severe symptoms of depression at baseline (β = - 0.30; 95% CI = - 0.43; - 0.16). Patients with moderate-to-severe symptoms of depression at baseline combined with those not living with a partner or a low/medium education level yielded the largest effect size through exercise (β = - 0.61; 95% CI = - 0.89; - 0.33 and β = - 0.37; 95% CI = - 0.57; - 0.17, respectively). Effects on anxiety symptoms were larger for patients with moderate-to-severe symptoms of anxiety at baseline (β = - 0.17; 95% CI = - 0.32; - 0.01) compared to those with no-to-mild symptoms. Sex, age, cancer type, BMI, and intervention-related variables did not moderate the exercise effects. CONCLUSION: The findings of this study highlight the heterogeneous response to exercise interventions across various patient subgroups. Patients with moderate-to-severe anxiety or depression, those with a low/medium education, and those not living together with a partner may particularly benefit.