This in-vitro study assessed micro shear bond strength of two different adhesive systems bonded on different dentin substrates. Fifteen freshly extracted human molars with coronal dentin caries were collected for this study. The roots were sectioned to expose the pulp chamber. The crown segment was then centrally glued using a cyanoacrylate adhesive to a circular Teflon plate of 10 mm diameter and 2 mm thickness. The occlusal portion of crown segments were ground flat to expose flat dentin surface parallel to the occlusal plan. Caries detector dye was used to identify caries-infected, caries-affected (CAD) and normal dentin (ND). For further confirmation, dye permeability test was applied to detect CAD. Specimens were divided into two main groups (30 each) according to the type of the adhesive system used: A1 (Adper Scotchbond Multipurpose adhesive) control group and A2 (Universal adhesive system). Each group was subdivided into two subgroups (15 specimens each) according to the type of dentin substrate used: D1 (ND) and D2 (CAD). Four resin composite microcylinders were built over each specimen in both substrates. A total of 60 composite microcylinders with prepared dentin surface containing both ND and CAD were used in the study. Each was polymerized using light curing unit. All specimens were subjected to micro-shear bond strength (μSBS) testing using a special universal testing machine (Model LRX-plus; Lloyd instruments Ltd., Ferham, UK). Data was then recorded, tabulated and statistically analyzed. Single bond Universal adhesive system (20.0 ± 96.7 MPa) showed statistically significantly lower mean μSBS than Adper Scotchbond Multipurpose adhesive systems (22.0 ± 10.4 MPa) (P=0.008). Micro-shear bond strength (μSBS) of ND substrate (24.3 ± 8.4 MPa) showed higher statistically significant values than that of CAD (19.4 ± 7.8 MPa) (P=0.001*). Two way ANOVA results showed statistical significant effect for the adhesive systems (Adper Scotchbond Multipurpose and Single bond Universal Adhesive) [p=0.008], dentin substrates (ND and CAD) [p<0.001] and the interaction between the variables had a statistically significant effect on the mean micro-shear bond strength. In conclusion, the type of substrate and bonding strategies affects the bonding performance and durability of restorations in dentistry