Cementing of indirect restorations with resin cements generally requires the pre-treatment of dentin with an adhesive. When dual-cured or chemical-cured resin cements are used with these single-step adhesives, incompatibility issues exist. This has resulted in manufacturers making chemical changes in their products. Kerr Dental markets a new resin cement, Nexus Third generation (NX3), which utilizes a proprietary redox system different from the second generation of composite luting agent (NX2). The aim of this study was to evaluate microtensile bond strength and mode of failure of NX3 and NX2 with two different adhesive systems (total-etch and self-etch) after 1 week and after 3 months of storage. Methods: Sixty-four non-carious teeth were sectioned to expose the dentin using a low-speed saw. Dentin surfaces were ground with 320-grit SiC paper. The adhesives Optibond Solo Plus (SOL), and Optibond All In One (AIO) were applied, and resin cements (NX2, NX3) were used to lute 4-mm composite discs to the treated dentin surfaces. Microtensile bond strength was determined at 1 week (IM) and after 3 months (3MON) of storage using a universal testing machine (MTS). All specimens were examined under the stereomicroscope to determine the mode of failure. Random specimens from each failure group were examined using scanning electron microscopy. Statistical Analysis: Comparisons between the treatment combinations for differences in microtensile bond strength were performed using Weibull-distribution survival analysis. Comparisons between the treatment combinations for differences in the failure mode were performed using Fisher’s Exact tests. The group NX3 SOL IM (30.5 MPa) had significantly higher bond strength than NX3 SOL 3MON (13.4 MPa); NX3 AIO IM (11.3MPa); NX3 AIO 3MON (8.2 MPa; NX2 AIO 3MON (5.8 MPa); NX2 SOL IM (6.3 MPa), and NX2 SOL 3MON (3.2 MPa). The group NX2 AIO IM (19.3 MPa) was not significantly different from NX3 SOL IM. The group NX2 SOL 3MON and group NX2 SOL IM had a significantly higher percentage of teeth with mixed failure than all of the other groups. None of the other groups had significantly different failure mode. The group NX3 SOL IM had 90-percent beam survival beyond 17 MPa, and NX2 AIO IM had 50 percent of beams surviving beyond 17 MPa, a better performance. For all the other groups, more than 50 percent of beams failed below 17 MPa. Results show high evidence of degradation for all groups considered in this investigation. The use of these types of cement adhesive combinations in clinical situations should be used with this understanding.