Capsosomes, polymer hydrogel capsules containing intact liposomal subcompartments, represent a promising platform toward the assembly of cell-like systems. Compartmentalized assembly plays a key role in the creation of therapeutic artificial cells, which focuses on enzymatic activities to degrade waste products or to support the synthesis of biomolecules. A fundamental aspect that governs the success of continuous enzymatic reactions in capsosomes is the long-term stability of the liposomal subunits within the polymer hydrogel capsules at physiological conditions, as they are subject to degradation in the presence of lipases. In this study, the outer membrane of the capsosomes was PEGylated by immobilizing graft copolymers of poly(methacrylic acid) (PMA) and poly(ethylene glycol) (PEG), and the fouling characteristics of this carrier system were investigated by incubation with bovine serum albumin. The influence of PEGylation on the stability of the liposomal subcompartments in the presence of phospholipases in different media was assessed. Diffusion of lipases across the multilayered membrane of the carrier capsules was hindered when the capsules were coated with PEG molecules. Furthermore, the rate of degradation of the liposomal subunits in PEGylated capsosomes was found to be three times higher when the subcompartments were “free-floating” (i.e., not membrane associated) in the capsules. The outlined surface modification of capsosomes contributes to the development of these systems toward functional therapeutic artificial cells.