Despite its economic and environmental advantages, the dry reforming of methane using supported Ni-based catalysts remains challenging due to problems of metal particle sintering and carbon deposition, which lead to loss in catalytic activity. In this study, different silica supports, containing 5 wt% nickel, were prepared and characterized by N2 sorption, XRD, TPR, and TEM/SEM, in addition to Raman and TGA/MS for the spent catalysts. Different synthesis conditions were thus varied, like nickel deposition method, nature of nickel precursor salt, conditions for thermal activation, and nature of support. The results showed that enhanced metal dispersion, good confinement, and efficient stabilization of the active phase inside the pores can be achieved by using a well-structured mesoporous support. Moreover, it was demonstrated that carbon resistance can be improved when small nickel particles are well confined inside the pores. The strategies that affect the final dispersion of nickel particles, their consequent confinement inside (or deposition outside) the mesopores and the resulting catalytic activity and stability include mainly the application of hydrothermal treatment to the support, the variation of the nature of nickel precursor salt, and the conditions for thermal activation. General guidelines for the preparation of suitable Ni-based catalysts highly active and stable for dry reforming of methane (DRM) are thus presented in this work.