This paper focuses on the improvement of the longevity and robustness of materials for sealing and plugging the upper portion of a deep borehole used for permanent isolation of high-level nuclear waste. Analytical models of porous and laminar flows show that even when materials have low intrinsic permeability, micron-sized cracks and gaps between the plug and rock (formed via chemical reaction, shrinkage, osmotic consolidation, etc.) significantly diminish the plug's sealing properties. On this basis, materials such as asphalt, traditional cements, and pure bentonite—which crack or shrink under certain conditions—are unfavorable. An ongoing test program has formulated expanding cement mixtures containing MgO to prevent such bypass flow. Furthermore, these findings support using stable, malleable, and low-permeability plug material (k ≤ 10−16 m2), such as a crushed rock (70%) and bentonite (30%) mixture. Alternative clays such as sepiolite could be blended with the bentonite to further reduce the potential negative effects of salinity on bentonite permeability. A bounding and analytical model of a scenario where radionuclide escape is determined by advection through the plug (and assuming a large and constant driving pressure) shows that a plug permeability of 10−16 m2 is sufficiently low to prevent advective transport of radionuclides from a depth of 2 to 3 km to the surface within the timescale of interest (∼1 million yr). Purely diffusive transport over the same distance, whether through the plug or host rock, is conservatively estimated to be significant only for a time >850 000 yr.