Background: Erythropoietin-resistant anaemia in hemodialysis patients is accompanied by poor outcomes. Malnutrition and inflammation impair effective erythropoiesis through various mechanisms and may cause erythropoietin resistance. In this study, we aimed to determine the effect of malnutrition inflammatory complex on erythropoietin resistance among patients on maintenance hemodialysis at Muhimbili National Hospital in Dar es Salaam, Tanzania. Materials and Methods: This was a hospital-based retrospective cross-sectional study involving 85 patients on maintenance hemodialysis. Participants’ information was collected and recorded in data collection tools; this information included clinical and physical information (body weight and height) and laboratory tests (complete blood count, serum albumin, C-reactive protein, transferrin, total iron, ferritin, and urea). Bodyweight and height were measured and body mass index calculated. Erythropoietin Resistance Index (ERI) was obtained as the weight-adjusted average weekly erythropoietin dose divided by hemoglobin level, while Malnutrition Inflammation Score (MIS) was used to determine Malnutrition Inflammation Complex Syndrome (MICS). Results: Eighty-five participants were recruited for this study, of which 76.5% were males and the mean age was 54.1 ± 13.2 years. MICS was noted in 50.6% participants. The overall mean weight-adjusted ERI of the study population was 20.6 ± 7.7 units/kg per g/dl. Patients with inflammation, MICS, and on long-term hemodialysis had significantly higher mean ERI. On multivariate analysis, ERI significantly correlated with MIS (p <0.01) in a dose-dependent manner. Conclusion: In hemodialysis patients, anaemia resistant to Erythropoietin therapy is linked to malnutrition inflammation complex syndrome. MICS needs to be appropriately treated to achieve target hemoglobin levels.