The current study aimed to compare the utilization efficiency of iron (Fe) feed additives from either bulk or nano sources in Nile tilapia, Oreochromis niloticus diets on growth, haematological, immunity, anti-oxidative, and intestinal topography capacities. Five isonitrogenous and isoenergetic diets were performed; the basal diet served as a control with no Fe added, whereas the experimental diets were shaped by adding bulk-Fe₂O₃ and nano-Fe₂O₃ to the basal diet to preserve Fe levels at 0.2 and 0.4 mg kg⁻¹, respectively. Results indicated that superior growth performance was recorded in fish-fed diets supplemented with 0.4 nano-Fe₂O₃ mg kg⁻¹ diet. In addition, the highest (P ≤ 0.05) survival rate, absorption area of villous (AAV), mucosal to serosal amplification ratio (MSR), and villi parameters (height and width) were noticed in fish fed diet enrichment with either bulk or nano-Fe₂O₃ source. However, the superiority observed in nano-Fe₂O₃ fish groups. Also, the highest values of plasma albumin, total protein, high-density lipoprotein cholesterol (HDL-C), white blood cells (WBCs), and lymphocyte absolute count (LYM) (P ≤ 0.05) recorded in fish fed a diet supplemented with nano-Fe₂O₃ versus the basal diet. Moreover, the highest values of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and plasma lysozyme activity (P ≤ 0.05) were observed in fish fed 0.4 mg/kg⁻¹ nano-Fe₂O₃, while the lowest value was recorded in fish fed the control diet. The best value of malondialdehyde activity (P ≤ 0.05) recorded in a fish-fed diet supplemented with 0.4 mg/kg⁻¹ nano-Fe₂O_3. The current findings emphasize the importance of including Fe to improve fish growth, immunity, antioxidant capabilities, and intestinal structure, primarily with a nano-Fe source, which demonstrated a more effective function in satisfying Nile tilapia dietary Fe requirements and improving the aforementioned parameters.