A comparative study of the effect of experimental conditions on the deep hydroconversion (up to 90%) of an heavy oil residue (Safaniya) in the presence of dispersed catalysts is reported. Severe thermal conditions are required to obtain a high conversion level. With molybdenum naphthenate as catalyst precursor, a low metal concentration (0.02 wt %) and a moderate hydrogen pressure level (7.5 MPa at cold) are efficient to maintain a low coke yield (2 wt %). In contrast to molybdenum naphthenate, a higher amount of phosphomolybdic acid is needed to achieve the same result. The reason for its weaker catalytic activity was attributed to a lower sulfidation state of the Mo catalyst, as outlined by physical characterization of the catalyst (XRD, HREM, STEM-EDX). This is in contrast to the rapid formation of numerous slabS of MoS2 obtained from molybdenum naphthenate. Nickel and cobalt naphthenate have been studied alone or in association with molybdenum naphthenate. As a pure compound, Mo metal seems to be more appropriate to perform the ultimate hydroconversion step while iron displays a lower activity. For nickel (or cobalt) molybdenum association, a synergism is observed, but the CoMo catalyst is more interesting in terms of conversion parameters and quality of the obtained products.