Methylmercury (MeHg), despite its low aqueous concentration, poses significant ecotoxicological risks in aquatic food webs. However, its dietary impacts on freshwater biota at environmentally relevant concentrations remain poorly understood. This study investigated bioaccumulation and molecular toxicity pathways in Dreissena polymorpha using transcriptomics, proteomics, metabolomics, and oxidative stress biomarkers following dietary exposure to inorganic Hg (IHg) and MeHg. Data revealed tissue-specific bioaccumulation patterns: the digestive gland, primary site of metal detoxification, accumulated higher total Hg (THg) concentrations, whereas gills showed higher %MeHg, suggesting an additional uptake pathway during filtration. Enzymatic activities and lipid peroxidation levels indicated the absence of oxidative stress, congruent with low exposure concentrations and bioaccumulation. At the molecular level, IHg primarily altered transcriptomic profiles, indicating a regulatory response, while MeHg induced broader proteomic and metabolomic disruptions. Enrichment analyses using The Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed distinct but overlapping pathways. IHg predominantly affected pathways related to amino acid metabolism, environmental information processing, and disease, while MeHg mainly affected energy, lipid, and carbohydrate metabolism, as well as immune and digestive system. These differences suggest contrasting toxicity pathways: IHg primarily disrupted cellular regulation and signaling, whereas MeHg targeted core metabolic and immune processes, reflecting its greater biological reactivity and bioaccumulation potential. Moreover, gills exhibited higher transcriptomic and proteomic responses, whereas the digestive gland showed higher metabolic adjustments, potentially reflecting differences in Hg exposure and tissue-specific Hg accumulation. By coupling functional biomarkers with multi-omics approaches, this study provides new insights into Hg toxicity in freshwater ecosystems and highlights the importance of tissue-specific assessments.