Biological and non-biological variables unrelated to acute myeloid leukemia (AML) preclude standard therapy in many settings, with “real world” patients under-represented in clinical trials and prognostic models. Here, using a case-based format, we illustrate the impact that socioeconomic and anthropogeographical constraints can have on optimally managing AML in 4 different healthcare systems. The granular details provided, emphasize the need for the development and targeting of socioeconomic interventions that are commensurate with the changing landscape of AML therapeutics, in order to avoid worsening the disparity in outcomes between patients with biologically similar disease.