Objective <p>To assess the influence of six-month water storage on the fracture resistance of molars receiving mesio-occluso-distal (MOD) nanoceramic CAD/CAM onlay restorations after cervical marginal elevation (CME) with different injectable restorative materials.</p> Materials and methods <p>Two hundred ten sound mandibular molars received standardized MOD onlay preparations with cervical margins extending 2&#xa0;mm apical to the cementoenamel junction (CEJ). Molars were randomly assigned into five groups (<i>n</i> = 42) according to the restorative materials used for CME: No-CME Group, control; CME-HVGI Group, highly viscous glass ionomer; CME-ICR Group, injectable composite resin; CME-RMGI Group, resin-modified glass ionomer; CME-BAIR Group, bioactive ionic resin. Immediate dentin sealing was performed on each molar before receiving nanoceramic-resin CAD/CAM onlay restoration. Each group was subdivided into two subgroups (<i>n</i> = 21) based on whether they underwent six months of water storage. All specimens were subjected to clinical simulation via thermo-mechanical loading, fracture resistance testing, and failure mode analysis.</p> Results <p>No statistically significant difference in fracture resistance was observed when comparing the tested CME groups to the control group after six months of water storage. Regarding failure mode, irreparable failure was significantly dominant, with no significant difference among all groups.</p> Conclusions <p>Six-month water storage had no adverse effect on the fracture resistance of teeth receiving nanoceramic onlay restorations, regardless of the type of cervical margin elevating material used.</p> Clinical relevance <p>The smoothly handled injectable restorative materials used for CME of molars with nanoceramic-resin CAD/CAM onlay restorations could endure humid conditions, exhibiting acceptable performance under compressive loading.</p>