The objective of this research is to develop catalysts for residue hydrocracking that can enhance the yield of the middle distillates. The support compositions were tailored to achieve optimal textural properties and the desired acidic function, and the catalyst hydrogenation function (i.e., the active metal, promoter, and their composition) was chosen to attain the required hydrotreating activity. The supports were synthesized by incorporating amorphous and crystalline SiO 2 in porous Al 2 O 3 . The catalysts, on the other hand, were prepared by coimpregnating the support extrudates with Mo and Ni. This study revealed that support textural properties are crucial for the diffusion and conversion of complex hydrocarbon molecules. The results also indicated that a balance between acidic and hydrogenation functions is essential for governing the conversion rate, product selectivity, and catalyst stability. The pore-size distribution of the composite support materials was designed to form a bimodal type of pore structure (10−20 and 200−100 nm) to allow complex molecules (i.e., asphaltene and resin) to diffuse into the pores and reach the inner catalytic and acidic sites, which are responsible for hydrogenation and hydrocracking activities, respectively. The texture, acidity, and reduction properties of the catalysts were measured by using different characterization techniques. Temperature-programmed reduction results indicated that the interactions between the active metals and supports differed with the support type and composition. The catalytic performances of the prototype catalysts were evaluated using a multiple microreactor fixed-bed unit that emulated the hydrotreating reactions in industrial hydroprocessing units (380−400 °C, 12 MPa, and 1 h −1 LHSV). The improved catalysts provided a middle distillate yield in the range of 20−25% and prominent hydrotreating activities under mild hydrocracking conditions.