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Poly(ethylene glycol)\u2010lipids ((PEG)\u2013lipids) have been central to this progress by providing steric stabilization, size control, and tunable biodistribution. However, PEGylation also introduces important limitations, including complement activation, pre\u2010existing and treatment\u2010induced anti\u2010PEG antibodies, and accelerated blood clearance, which increasingly constrain repeated and long\u2010term dosing strategies. This review focuses on recent advances in PEG\u2010alternative LNP designs, including non\u2010PEG polymers, zwitterionic and biomimetic lipids, polypeptides, and structurally modified PEG analogues. We compare how polymer chemistry, anchor geometry, and grafting architecture influence LNP formation, physicochemical properties, biodistribution, cellular uptake, and immunological outcomes. 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