Background: There is evidence from RCTs demonstrating that our current models of CGA guided care can reduce treatment related toxicity effectively. However, it is unclear if CGA guided care can improve OS and HRQL. We aimed to determine the effect of CGA guided care compared with usual care on OS and HRQL. Methods: We searched MEDLINE, EMBASE, CENTRAL and CINAHL from date of inception to October 2022 for RCTs comparing CGA guided care with usual care for patients with cancer who were 60 years old and greater on OS and HRQL. We assessed the risk of bias using Cochrane ROB 2 tool. We performed the meta-analysis using random-effects models. The I² statistic was adopted to assess heterogeneity between studies. We adopted the Synthesis without meta-analysis approach for data not amenable for meta-analysis. The certainty of evidence was rated using the GRADE approach. This study is registered with Cochrane Database of Systematic Reviews (DOI: 10.1002/14651858.CD014875). Results: We found 15 eligible RCTs including 3507 participants. There are variations in types of CGA used with 4 trials using CGA to recommend oncology treatment regimen and 10 trials making no recommendation on oncology treatment. The implementation of CGA recommendations were carried out by a geriatrician in 14 trials, but by the primary oncologist in 1 trial. Six, five and four RCTs were judged to have low, unclear and high risk of bias respectively. Eleven and six RCTs reported OS and HRQL outcomes respectively. There was no significant difference between CGA guided and usual care for OS (Hazard Ratio 1.02, 95% CI (0.90 to 1.15), I² = 0%; moderate certainty). There was significant variation in the measurement of HRQL in terms of instruments, summary measures and time points. EORTC QLQ C30 and ELD 14 were used in 3 RCTs. The effects of CGA guided care on HRQL were inconsistent. Two trials using FACT-G or Elderly Functional Index (ELFI) reported significant improvement in HRQL at 3 and 6 months post randomization. Meta-analysis of the mean difference in the change of the EORTC QLQ C30 and E14 HRQL scores relative to baseline at 6 months post randomization demonstrated no significant difference between CGA guided and usual care for HRQL across various domains (moderate certainty evidence). Conclusions: The current models of CGA guided care did not improve OS and had variable effects on HRQL when compared to usual care in older patients with cancer. The inconsistent effects of CGA guided care on HRQL suggest that CGA guided care may have more significant effects on the social and functional outcomes domains, aspects of HRQL that is predominantly measured in FACT-G and ELFI score respectively. There is also heterogeneity in how CGAs are performed and implemented. Future research should focus on developing new models of CGA guided care to improve OS and HRQL.