Variation in water temperature has a big impact on fish physiology, behavior, growth, and other biological processes. The current perspective aimed to assess the ameliorative effects of Spirulinaco-enzyme Q10 nanoemulsion (SCN) dietary inclusion on reared Nile tilapia (Oreochromis niloticus) health aspects under heat stress conditions (32 °C). A random design was used to establish 5 groups of Nile tilapia (n=225), each consisting of 15 fish in triplicates. After being given a baseline diet, the 1st (C25) and 2nd (SCN0) groups were raised at 25 °C and 32 °C respectively and supplemented by a basal diet. Diets supplemented with a10, 20, and 40 mg/kg diet were given to groups 3 (SCN10), 4 (SCN20), and 5 (SCN40), respectively, which were raised at 32 °C for 60 days. At the termination of the 60-day session, growth metrics, and immunological biomarkers were assessed. Tissue specimens were also obtained for further assessment of the antioxidant status and histopathological alterations. A subsequent bacterial challenge with Streptococcus agalactiae was performed, where mortalities, clinical symptoms, and postmortem lesions were investigated. As per the results of the investigation, dietary incorporation with SCN40 followed by SCN20 significantly promoted growth metrics and immunological biomarkers, where the lowest records were noted in SCN0. Tissue antioxidants (SOD, GST, and CAT) showed notable improvement in SCN40, which also expressed the lowest MDA value compared to SCN0. Nonetheless, oxidative stress mediators and lipid peroxidation markers revealed a marked decline in SCN-fortified groups in a concentration-associated pattern compared with the SCN0 group. Histopathological evaluation of liver, intestine, and spleen tissues revealed a noticeable improvement and almost restoration of the normal tissue architecture in the SCN20 and SCN40 groups. Following the Streptococcus agalactiae challenge, Nile tilapia survivability was significantly higher in SCN40 (80%) than in SCN20 (74%). Taken together, SCN, especially at 20 and 40 mg levels, demonstrated its valuable impact on mitigating heat stress in the Nile tilapia