Background: Symptom management is a critical aspect of comprehensive palliative care for people with advanced cancer. Web and mobile-based applications are promising e-Health modalities that can facilitate timely access to symptom management interventions for this population Aim: To evaluate the efficacy of web and mobile-based symptom management interventions in alleviating physical symptom burden in people with advanced cancer. Design: A systematic review and meta-analysis was conducted. PROSPERO ID = CRD42020155295. Data sources: We searched databases including PubMed, PsycINFO, and CINAHL from 1991 until 2019. Inclusion criteria were: adults with advanced cancer, web or mobile-based interventions targeting symptom management, and report of physical symptom data. Risk of bias was assessed using the ROBINS-I and RoB2. Using RevMan, standardized mean difference (SMD) and 95% confidence intervals were calculated. Heterogeneity was assessed using the I 2 statistic. An assessment of interventions was conducted by evaluating the delivery mode, duration, and evaluation of application feature and theoretical elements. Results: A total of 19 studies are included in the systematic review and 18 in the meta-analysis. Majority of the studies were deemed to have high risk of bias. Most of the interventions used a web-application for delivering their education ( n = 17). While the interventions varied regarding duration and content, they were mainly guided by a symptom management theory. Web and mobile-based interventions significantly improved the overall physical symptom burden (SMD = −0.18; 95% CI = −0.28 to −0.09; I 2 = 0%; p = 0.0002). Conclusions: Web and mobile-based intervention are efficacious in decreasing the overall physical symptom burden in people with advanced cancer.