This study aimed to investigate the effects of the probiotic Betaplus^® and prebiotic Technomos^® as feed additives for Nile tilapia in terms of growth performance, health profiles, and resistance to infection with Aeromonas hydrophila and Pseudomonas fluorescens. A total of 960 healthy juvenile Nile tilapia (1.5 ± 0.01 g) were randomly divided into four experimental variants with three replicates for each variant. Fish were fed a commercial diet (control group, V₀), supplemented with BetaPlus^® probiotics–1% × BW (V₁), TechnoMos^® prebiotics–1% × BW (V₂), and with BetaPlus^® probiotics and TechnoMos^® prebiotics in a ratio of 1:1% × BW (V₃). Results on growth performance showed the best values in the probiotic variant, correlated with the health profile and the relative survival percentage after the challenge test with A. hydrophila and P. fluorescens. Similarly, the effects of dietary supplementation with probiotics and prebiotics on physiological conditions also recorded beneficial results in the synbiotic variant, where a high survival percentage was obtained after infection with the two pathogenic bacteria. In conclusion, the results of this study indicate that dietary supplementation with feed additives consisting of mentioned probiotics, prebiotic, and their combination as synbiotics has the potential to promote growth performance, improving tilapia immunity and increasing survival after the challenge test.