The mining industry is characterized by a high consumption of energy due to the wide diversity of processes involved, specifically the transportation of ore slurry via pipeline systems. This study investigates the relationship among the variables that define the slurry transportation system to minimize the power requirements and increase energy sustainability. The energy indicator (I), the criterion used for the energy assessment of three different pumping system layouts, was computed via numerical simulation. Optimization of response I was carried out through a statistical technique in the design of the experiment. In the study, four variables were defined to describe the slurry transportation systems, two of which are associated with the piping system (length L and diameter D); the other two are related to the slurry pattern (the volumetric concentration Cv and granulometry D50). The results show that all variables are statistically significant relative to the indicator I, with L having the greatest amplitude of variation in the response, increasing the energy indicator by approximately 60%. Likewise, the decrease of the D50 from 300 µm to 100 µm produces an average decrease of I of 24%. Moreover, the interaction among the factors indicates that two pairs of factors are correlated, namely D50 with L and D with L. Finally, a predictive model obtained a fit that satisfactorily relates with the numerical data, allowing, in a preliminary way, to identify the minimum power requirement in iron ore slurry pipeline systems.