Sweet cherry generates large amounts of by-products within which pomace can be a source of bioactive phenolic compounds. Commonly, phenolic compounds have been obtained by conventional extraction methodologies. However, a significant fraction, called non-extractable polyphenols (NEPs), stays held in the conventional extraction residues. Therefore, in the present work, the release of NEPs from cherry pomace using pressurized liquid extraction (PLE) combined with enzyme-assisted extraction (EAE) using PromodTM enzyme is investigated for the first time. In order to study the influence of temperature, time, and pH on the NEPs extraction, a response surface methodology was carried out. PLE-EAE extracts displayed higher TPC (75 ± 8 mg GAE/100 g sample) as well as, PA content, and antioxidant capacity than the extracts obtained by PLE (with a TPC value of 14 ± 1 mg GAE/100 g sample) under the same extraction conditions, and those obtained by conventional methods (TPC of 8.30 ± 0.05 mg GAE/100 g sample). Thus, PLE-EAE treatment was more selective and sustainable to release NEPs from sweet cherry pomace compared with PLE without EAE treatment. Besides, size-exclusion chromatography profiles showed that PLE-EAE allowed obtaining NEPs with higher molecular weight (>8000 Da) than PLE alone.