Background: Many patients receiving myelosuppressive chemotherapy are at an intermediate risk (10-20%) of developing FN. In this setting, clinical practice guidelines recommend an individualized approach towards MGF prophylaxis based on regimen and patient-specific FN risk factors. The purpose of this review is to summarize and describe the real-world MGF prophylaxis patterns, patient-specific risk factors, and FN outcomes in patients receiving chemotherapy at intermediate risk of FN. Methods: We searched the MEDLINE database (PubMed) for peer-reviewed published articles using the keywords “primary prophylaxis,”“febrile neutropenia,” and “intermediate risk” from 2000-2020. Articles were included if they were cohort or case control studies, and excluded if the data were derived from clinical trials. Studies from outside the United States or where the methods cannot be verified were also excluded. Results: Out of 131 studies identified, 7 met the inclusion/exclusion criteria after review. Most studies included adult cancer patients diagnosed with breast, lung or colorectal cancer receiving chemotherapy identified using public/private insurance claims or electronic medical records. In the 2000s, MGF prophylaxis rates were around 17-22% in patients receiving intermediate-risk regimens; while in 2010s, the prophylaxis rate increased to > 50%. Patient-specific FN risk factors were prevalent, but MGF primary prophylaxis rates among those receiving intermediate risk regimens were generally low (around 24-28%); approximately 25% of patients with > 1 FN risk factor received primary prophylaxis. Primary prophylaxis rates differed by tumor type; breast cancer had the highest rate (~46%), followed by non-small cell lung (~24%), and colorectal (~8%). FN incidence varied among patients with FN risk factors (~7 to 29%) across intermediate risk regimens, and the relative risk of FN (vs. those without risk factors) ranged from 1.1 to 2.2. Conclusions: Although historically low, MGF prophylaxis in patients receiving intermediate risk regimens has been increasing. Patient FN risk factors were widespread and associated with increased FN incidence. Since appropriate primary prophylaxis in patients at intermediate-risk could potentially improve population-based FN-related outcomes, future studies should focus on whether biosimilar MGFs as primary prophylaxis are cost-effective and could better optimize the care reflected in current MGF practice guidelines.