This study aims to examine the effects of supplementing male rabbit diets with nanoparticles of zinc oxide (Nano-ZnO) and Acacia nilotica fruit powder (ANFP) on production sustainability under hot climatic conditions. Eighty Californian male rabbits aged 40 days old (average body weight 738.5  11 g) were divided into four treatment groups and administered one of the following diets: control diet, Nano-ZnO (50 mg/kg), ANFP (5 g/kg), or a combination of Nano-ZnO (50 mg/kg) and ANFP (5 g/kg) for a period of 60 days. Each of the 20 rabbits used in a treatment was regarded as a replicate. The results showed that adding Nano-ZnO and ANFP individually or in combination to rabbits’ diets improved (p < 0.05) growth performance in comparison to control. In addition, zinc contents in serum or the testis tissues in the Nano-ZnO- and ANFP-treated rabbits were significantly greater (p < 0.05) than those in the control group. In addition, serum levels of creatinine, alanine aminotransferase, and aspartate aminotransferase were decreased (p < 0.05) by supplementation of Nano-ZnO, ANFP, or their combination. Carcass criteria did not differ among the treatments. Overall, the findings of the present study indicate that rabbits fed diets containing Nano-ZnO and ANFP, as well as their combination, showed improvements in growth performance, kidney and liver functions, as well as zinc retention in tissues under hot climatic conditions. The combination of Nano-ZnO and ANFP exhibited the best performance in the rabbits. More research on the synergistic effects of Nano-ZnO and ANFP in the sustainable production of rabbit meat is required.