Objectives: This study aims to assess and compare the micro-shear bond strength (μSBS) of a novel resin-modified glass-ionomer luting cement functionalized with a methacrylate co-monomer containing a phosphoric acid group, 30 wt% 2-(methacryloxy) ethyl phosphate (2-MEP), with different substrates (dentin, enamel, zirconia, and base metal alloy). This assessment is conducted in comparison with conventional resin-modified glass ionomer cement and self-adhesive resin cement. Materials and methods: In this in vitro study, ninety-six specimens were prepared and categorized into four groups: enamel (A), dentin (B), zirconia (C), and base metal alloys (D). Enamel (E) and dentin (D) specimens were obtained from 30 human maxillary first premolars extracted during orthodontic treatment. For zirconia and metal alloys, 48 disks were manufactured using IPS e.max ZirCAD through dry milling and Co–Cr powder alloy by selective laser milling. Each group was further subdivided into three subgroups (n = 8) according to the luting cement used: (1) Fuji PLUS resin-modified glass ionomer luting cement (FP) as a control cement, (2) modified control cement (eRMGIC), and (3) RelyX U 200 (RU 200) self-adhesive resin cement. The two-way analysis of variance and Tukey’s HSD were used to assess the data obtained from measuring the μSBS of the samples. Results: The results of this study showed that the mean μSBS values of eRMGIC were statistically higher compared to FP in all tested groups (p < 0.001). The mean μSBS results of eRMGIC were non-significantly different from those recorded by RU 200 for all substrates except for the dentin substrate, where the RU200 cement produced significantly higher strength (p < 0.001). The failure modes were limited to a combination of mixed and adhesive failures without pure cohesive failure. Significance: The functionalization of FP with an organophosphorus co-monomer (2-MEP) directly affects the adhesion performance of the functionalized cement, which may be utilized to develop a new type of acid-base cement. It exhibited a performance comparable to that of resin-based cement and should serve well under different clinical conditions.