The resonance self-shielding effects in heterogeneous fissile breeding systems have been investigated. In media having peaked resonance cross sections, the influence of heterogeneities is manifested in the energy and space neutron flux depressions. The outcomes of numerical calculations performed for various pellet sizes and fissile material concentrations are shown in the form of “het-to-hom” ratios of the results obtained by considering normalized heterogeneities in relation to those accounting for self-shielding in respective, computationally homogenized mixtures. The observed reduction in fissile breeding and the increase in tritium breeding, 233U fissions, and parasitic absorptions are of the order of several tens of percent, depending on the fertile content. It is emphasized that neglecting heterogeneities leads to serious errors and nonoptimum designs, thus proving to be inadmissible in neutronic calculations for emerging nuclear energy systems.