Background: Calcium-silicate-based cements (CSC) have gained an increasing scientific and clinical relevance, enabling more conservative approaches, namely pulp preservation and regeneration therapies. This research aims to study the influence of four clinical variables on the interfaces between CSC and composite adhesive restoration, concerning shear bond strength (SBS) and ultra-morphological patterns. Methods: SBS tests were performed in 320 specimens divided in 16 groups (n = 20) according to: two CSC (NuSmile® NeoMTA, BiodentineTM); two adhesive systems (ClearfilTM SE Bond 2 (CSEB2), ClearfilTM Universal Bond Quick (CUBQ)); optional application of an additional hydrophobic bonding layer (HBL); two restoration times (immediate, seven days). Scanning electron microscopy (SEM) was performed to conduct the ultra-morphology interface analysis in 32 deciduous molars prepared and randomly allocated into the 16 groups. Results: Globally, SBS tests showed higher bond strength of CUBQ compared to CSEB2 (p < 0.001), as with an additional HBL application (p = 0.014) and delayed restoration (p < 0.001). SEM showed the interpenetration between adhesive systems and CSC forming a hybrid layer, whose depth and thickness depended on the restoration time and adhesive strategy. Conclusions: The independent clinical variables adhesive system, application of an additional HBL and restoration time affected the bond performance and ultra-morphological interface between composite adhesive restoration and CSC.