Background: The number of asymptomatic patients diagnosed with metastatic cancer is increasing. This is mostly due to increased used of imaging, especially for screening and during follow-up. Traditionally, chemotherapy is started immediately in these patients, but some argue that withholding chemotherapy until symptoms occur may be beneficial for patients, especially in terms of quality of life. However, the impact on survival and quality of life is unknown. The aim of this study is to give an overview of delayed versus immediate chemotherapy in asymptomatic patients with metastatic cancer. Methods: We systematically searched PubMed, EMBASE (Ovid), and Cochrane for studies investigating the timing of start of chemotherapy in asymptomatic patients with metastatic cancer. Primary outcome was overall survival (OS). Secondary outcomes included quality of life (QOL) and toxicity. A meta-analysis was performed on OS, including all studies that compared direct versus delayed chemotherapy. Quality of life was described using the global health status derived from the EORTC-QLQ-C30 questionnaire evaluated in the studies. Results: Four randomized controlled trials and one retrospective study with overall 919 patients were included. The studies considered colorectal cancer (n = 3), ovarian cancer (n = 1), and gastric cancer (n = 1). The median OS varied from 11.9 to 25.7 months in the immediate treatment group versus 9.0 to 27.1 months in the delayed group. A pooled analysis demonstrated no significant differences in OS between the groups (pooled HR 1.05, 95% CI 0.90-1.22, p = 0.52). Quality of life was evaluated in three studies and suggested a better QOL in the delayed treatment group. In two studies including colorectal cancer patients the global health status in the immediate treatment group was lower at all time-points compared to the delayed treatment group, with no significant differences in any of the separate domains. In the study evaluating ovarian cancer patients, among others, the time median time spent in good global health score was lower in the immediate treatment group. Toxicity was compared between the two groups in one study, and this showed no significant differences. Conclusions: This systematic review with meta-analysis on timing of start of chemotherapy in asymptomatic patients with metastatic cancer suggests that a delayed start of chemotherapy, as compared to immediate start, does not result in worse OS, while it may better preserve QOL. Future randomized trials, with specific emphasis on quality adjusted life years are needed.