This study aimed at evaluating the shear bond strength (SBS) of modern self-adhesive resin cements and resin-modified glass ionomer cements applied to different prosthetic substrates. Zirconia, lithium-disilicate glass-ceramic and a noble metal alloy were used as bonding substrates. They were all sand-blasted with alumina, while LD was further etched with 9.6% hydrofluoric acid (10 s). A light-curing resin-modified glass ionomer cement (3M-GIC: Ketac Cem Plus) and a self-curing resin-modified glass ionomer cement (GC-GIC: FujiCEM 2) were compared to self-adhesive resin cements (PAN: Panavia SA Universal) and (3M-RES: Rely X Unicem 2). Ten specimens for each substrate were produced and up to five cylinders of each cement were bonded to each substrate. The shear bond strength (SBS) was evaluated after 24 h or after thermocycling (TC) aging (5000 cycles). The data was statistically analysed by two-way ANOVA and Student–Newman–Keuls test (α = 0.05). Failure modes were analysed through stereoscopic microscopy. The greatest SBS was attained with PAN, whilst 3M-GIC showed the lowest SBS and failed prevalently in adhesive mode. No difference in SBS was observed between GC-GIC and 3M-RES. After TC aging, all cements showed significant drop (p < 0.05) in SBS, but PAN showed the greatest SBS. Reliable bond strength to prosthetic substrates can be achieved with specific universal resin-luting cements and may be an alternative to glass ionomer cements when luting alloy substrates.