This study investigates the effect of the response surface method (RSM) on heat sinks designed in block types using various fluids. The RSM method is applied to the data obtained from heat sinks designed in block types using water, mono-nanofluids, and hybrid nanofluids placed in both vertical and horizontal directions. The data were collected under five different pressure boundary conditions and applied to 144 data sets. The results show that the R2 values for thermal resistance (Rth), CPU mean temperature (Tm) and Performance Evaluation Criterion (PEC) in horizontal arrangements are 99.21%, 99.21% and 99.37% respectively. The Box-Behnken method was used to analyze the design parameters and derive equations for seven different parameters: density, viscosity, specific heat, thermal conductivity, block thickness, block distances, and inlet pressure boundary conditions. Equations were used to determine the average CPU temperature, thermal resistance, and Performance Evaluation Criteria (PEC). The R2 values for vertically oriented geometries were 97.66%, 97.66%, and 98.45%, indicating a strong correlation between the results obtained from FLUENT and the ANOVA statistical results. The linear, square, and cubic effects of each variable significantly affected each solution. The study concludes that the RSM method has a significant impact on heat sinks with higher R2 values in horizontal arrangements and a higher distance between blocks