This experiment was conducted to optimize temperature and time for hot smoking of Nile Tilapia in order to get the most nutritive quality. Three levels of smoking temperature (80 ± 3°C, 90 ± 3°C and 100 ± 3°C) and time (2:00, 2:30 and 3:00 hours) were used. Accordingly, Face centered central composite design using Design expert (version 7.0.0., Stat-Ease, Minneapolis, MN) was used to optimize and evaluate main effects, interaction effects and quadratic effects of smoking temperature and time on gross energy value and overall sensory acceptability. A Multiple Linear Regressions Analysis (MLRA) was performed to determine all the coefficients of constant, linear, quadratic and interaction terms using least square minimization to fit the intended model to the collected data. The lack of fit test was used to evaluate the fitness of the generated model using coefficient of determination (R2). The adequacy of the model was justified through Analysis of Variance (ANOVA).The result show that all the built polynomial equations were found to be statistically non-significant as determined by ANOVA, lack of fit is nonsignificant and the model is less adequate to sufficiently describe the experimental data. The numerical optimization using desirability approach of all combination resulted in smoking temperatures and times were found to be optimum to produce good gross energy value and sensory acceptability of smoked fish. From model summary statistics, a negative predicted R2 implies the overall/grand mean is a better predictor of gross energy value and overall sensory acceptability than the current model. Accordingly, Nile Tilapia (Oreochromis niloticus) smoked at 80 ± 3°C for 2:00 and 80 ± 3°C for 3:00 hour possessed the highest gross energy value (kcal) for non-dried and pre-dried respectively and fish smoked at 100 ± 3°C for 2 and 3 hours and 90 ± 3°C for 2 and 3 hours possessed highest overall sensory acceptability for non-dried and pre-dried respectively.