Introduction <p>Multi-cancer detection (MCD) tests currently being tested in clinical trials may be a scalable, convenient means to improve cancer screening, yet little is known about the potential clinical and psychosocial consequences of doing so in underserved communities.</p> Objective <p>To summarize the current literature examining potential clinical and psychosocial outcomes and consequences for MCD testing in underserved populations.</p> Methods <p>We searched and then reviewed articles from five databases: PubMed, Embase, Scopus, Web of Science, and Cochrane. For inclusion, studies had to primarily focus on MCD testing within underserved populations. Out of 376 articles identified, 29 met inclusion criteria.</p> Results <p>Financial constraints were the most frequently cited barrier (<i>n</i> = 23). 24 articles mentioned clinical consequences and nine mentioned psychosocial consequences, with the most common being lower rates of cancer screening with proven existing recommended tests (<i>n</i> = 10) and emotional stress, worry, and anxiety (<i>n</i> = 11), respectively. Many expressed concerns about underrepresentation in clinical trials.</p> Conclusions <p>The review highlights common potential clinical consequences as well as important factors underserved populations may face if/when MCD testing is implemented in their healthcare. Future prospective studies, experimental and observational, should intentionally include underrepresented patient populations to better understand and address these challenges.</p>