Biorefining of bilberry pomace using innovative technologies such as microwave hydrodiffusion and gravity extraction (MHG) and ultrasound-assisted extraction (UAE) with different concentrations of ethanol/water as the solvent was established. Bead milling was also utilized in this sequential extraction scheme to remove the lipophilic fraction. The solubility index of target polyphenols was predicted using a computational tool (COSMO-RS) and compared to experimental results obtained by in vitro antioxidant activity assessments. MHG extracts obtained using microwave power of 2 W/g had the highest Folin–Ciocalteu reducing capacity (43.46 ± 0.48 mg gallic acid equivalent (GAE)/g of extract), total flavonoid (4.17 ± 0.04 mg quercetin equivalents (QE)/g of extract), total monomeric anthocyanin content (12.19 ± 0.13 mg delphinidin-3-O-glucoside equivalents (D3GE)/g of extract), and radical scavenging capacity (22.64 ± 2.23 mg trolox equivalents (TE)/g of extract). In UA ethanol/water extracts, the highest flavonoid (10.41 ± 0.08 mg QE/g of extract) and anthocyanin content (12.19 ± 0.51 D3GE mg/g of extract) was present in ethanol (100%), these results were in good correlation with computational predictions. The lipid fraction recovered from pomace using bead-milling extraction was mainly composed of oil rich in polyunsaturated linoleic and linolenic acids.