Background: Cancer patients are more susceptible to severe complications and high mortality from Coronavirus disease 2019 (COVID-19). There is no solid evidence of whether anti-cancer therapy plays a significant role in increasing COVID-19 severity or mortality in cancer patients. Also, there is no definitive US guideline on how to justify anti-cancer treatment in cancer patients with COVID-19. Therefore, we conducted a systematic review and meta-analysis of the effect of anti-cancer therapy in cancer patients infected with COVID-19. Methods: A systematic search of Pubmed and Cochrane databases was conducted and two reviewers screened the articles independently. Previously published review articles were also evaluated to include the studies not identified in the Pubmed and Cochrane. Any clinical study of adults was included if it contains data on mortality or COVID-19 severity in cancer patients, both treated and untreated within 3 months before COVID diagnosis. Pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated by employing the random-effects model, Mantel-Hazel method. Review Manager (RevMan) Version 5.4, The Cochrane Collaboration 2020 was used. Results: Out of 1690 studies identified from the databases and 8 studies from previous review articles, 22 studies (4777 patients) were included for analysis of the effect on mortality, and 12 studies (1898 patients) were included for the effect on COVID-19 severity. There were no significant differences in mortality between patients receiving anticancer treatment and those not (OR 1.17, 95% CI: [0.92-1.49], I2 = 56%, p = 0.21). There were no significant differences in mortality between patients receiving chemotherapy and those not receiving anticancer treatment but there was a trend towards higher mortality in patients receiving chemotherapy. (OR 1.43, 95% CI: [0.96-2.15], I2 = 68%, p = 0.08). There were no significant differences in COVID-19 severity between patients receiving anticancer treatment (OR 1.43, 95% CI: [0.96-2.15],, I2 = 10%, p = 0.27) and those not and between patients receiving chemotherapy and those not receiving anticancer treatment (OR 1.17, 95% CI: [0.83-1.65], I2 = 10%,p = 0.36). Conclusions: The results of our study were similar to previous meta-analyses despite more clearly defining anti-cancer treatment recency (anti-cancer treatment within 3 months before COVID diagnosis). There was low heterogeneity among studies for COVID-19 severity but high heterogeneity among studies for mortality. Most of the studies we analyzed were conducted in the 2020 and pre-vaccine era. Novel COVID-19 treatments and vaccination will likely affect outcomes in cancer patients with or without anti-cancer treatment. We need updated research and more detailed guidelines on anti-cancer therapy in COVID-19 infections.