This study investigated the parasitic infestations among 300 tilapia fish (Oreochromis niloticus and O. aureus) and the water parameters of sixty water samples from Damietta Governorate. Clinically, affected fish displayed emaciation and opacity in the eye with focal external hemorrhages. The detected parasites were protozoa (Chilodonella hexasticha), monogenea (Cichlidogyrus tilapiae), and digenetic trematode metacercaria (Heterphyes spp, Haplorichis spp, Clinostomum tilapiae, Euclinostomum heterostomum, Diplostomum spathacaum, Centrocestus formosanus, and other unidentified metacercaria). The total infestation rate was 60%, (66.7% in O. niloticus, followed by 53.3% in O. aureus). Summer was the season with the highest infestation (80% in O. niloticus and 64% in O. aureus). Water parameters such as visibility, oxygen levels, pH, and total alkalinity exhibited a significantly negative correlation with parasitic infestation. Conversely, water temperature, unionized ammonia, and NO3-N concentrations displayed a positive correlation. The occurrence of parasitic infestation increased in highly polluted water, where zinc exhibited a notable positive correlation with its infestation. Histopathological examinations of tilapia species exhibited various pathological alterations. C. hexasticha embedded within the secondary lamellae of the gills that were surrounded by a connective tissue capsule. Additionally, C. tilapiae was identified within the musculature, situated between muscle bundles.  Parasitic cysts of Haplorchis spp. were encapsulated with connective tissue that caused pressure atrophy in adjacent hepatocytes. Furthermore, E. heterostomum, was identified in renal tissue. Thus, this study affirmed the connection between parasitic prevalence and changes in the aquatic environment. Understanding these dynamics is essential for managing and mitigating the impact of climate change on the epidemiological maps for parasitic diseases in fish populations, ultimately contributing to disease minimization and the promotion of sustainability in aquaculture.