This study aimed to assess the impact of seasonal changes on heavy metal concentrations in water and their effects on Nile Tilapia (Oreochromis niloticus) liver and gill histomorphology in Burullus Lake, Egypt in 2021. Six designated points were selected for water and fish (length ±5cm) sampling in both summer and winter. The results indicated that Iron (f.e) had the highest overall levels across all seasons and sites, while Zinc (Zn), Lead (Pb), Copper (Cu), and Cadmium (Cd) showed variations. Notably, Pb, Cu, and Cd exhibited the widest ranges in concentration. Bioaccumulation of heavy metals in O. niloticus muscles revealed that Zinc concentrations were significantly highest in summer and winter at Site 3 (p < 0.05), while Iron levels were significantly highest in winter and lowest in summer (p < 0.05). Cadmium content varied, and lead concentrations remained low level. Histomorphological analysis of Nile tilapia liver and gills showed significant differences between summer and winter months. In summer, the liver exhibited severe hepatocyte degeneration, pancreatic blood vessel congestion, and pancreatic acinar cell degeneration, affecting liver development stages. Winter liver histomorphology was comparatively better than summer but showed some signs of central vein congestion, mononuclear cell infiltration, vacuolar degeneration, hypertrophy, and pancreatic acinar cell degeneration. Gill histomorphology in summer showed mild to severe congestion, hyperplasia, desquamation, edema, fusion, and degenerative changes, while winter gills displayed mild degeneration in secondary lamellae, hyperplasia of the epithelial lining, congested branchial blood vessels, and interstitial edema. Conclusively, these findings highlight the impact of seasonal changes on the health of Nile tilapia, with more severe consequences observed during the summer months.