Patients with cancer and their families often experience significant distress and deterioration in their quality of life. Psychosocial interventions were used to address patients' and families' psychosocial needs. Digital technology is increasingly being used to deliver psychosocial interventions to patients with cancer and their families. A systematic review and meta-analysis were conducted to review the characteristics and effectiveness of digital health interventions on psychosocial outcomes in adult patients with cancer and their family members. Databases (PubMed, Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, ProQuest Dissertations and Theses Global, and ClinicalTrials.gov) were searched for randomized controlled trials (RCTs) or quasi-experimental studies that tested the effects of a digital intervention on psychosocial outcomes. The Joanna Briggs Institute's critical appraisal checklists for RCTs and quasi-experimental studies were used to assess quality. Standardized mean differences (ie, Hedges g) were calculated to compare intervention effectiveness. Subgroup analysis was planned to examine the effect of delivery mode, duration of the intervention, type of control, and dosage on outcomes using a random-effects modeling approach. A total of 65 studies involving 10,361 patients (mean 159, SD 166; range 9-803 patients per study) and 1045 caregivers or partners (mean 16, SD 54; range 9-244 caregivers or partners per study) were included in the systematic review. Of these, 32 studies were included in a meta-analysis of the effects of digital health interventions on quality of life, anxiety, depression, distress, and self-efficacy. Overall, the RCT studies' general quality was mixed (applicable scores: mean 0.61, SD 0.12; range 0.38-0.91). Quasi-experimental studies were generally of moderate to high quality (applicable scores: mean 0.75, SD 0.08; range 0.63-0.89). Psychoeducation and cognitive-behavioral strategies were commonly used. More than half (n=38, 59%) did not identify a conceptual or theoretical framework. Most interventions were delivered through the internet (n=40, 62%). The median number of intervention sessions was 6 (range 1-56). The frequency of the intervention was highly variable, with self-paced (n=26, 40%) being the most common. The median duration was 8 weeks. The meta-analysis results showed that digital psychosocial interventions were effective in improving patients' quality of life with a small effect size (Hedges g=0.05, 95% CI -0.01 to 0.10; I2=42.7%; P=.01). The interventions effectively reduced anxiety and depression symptoms in patients, as shown by moderate effect sizes on Hospital Anxiety and Depression Scale total scores (Hedges g=-0.72, 95% CI -1.89 to 0.46; I2=97.6%; P<.001). This study demonstrated the effectiveness of digital health interventions on quality of life, anxiety, and depression in patients. Future research with a clear description of the methodology to enhance the ability to perform meta-analysis is needed. Moreover, this study provides preliminary evidence to support the integration of existing digital health psychosocial interventions in clinical practice. PROSPERO CRD42020189698; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=189698.