This study aimed to synthesize functionalized nanosupports via emulsion polymerization to develop new promising nanobiocatalyts via enzyme immobilizations. The co‐monomers methyl methacrylate, divinylbenzene and the epoxy monomer glycidyl methacrylate (GMA) were used. The performance of the nanobiocatlysts was evaluated in hydrolysis and esterification reactions after the immobilization of lipase B from Candida antarctica (CAL B). Firstly, the nanosupports functionalized in situ with 25% and 50% w/w of GMA were successfully synthesized. In esterification reactions, the nanobiocatalysts containing 25% (w/w) of GMA were more active, achieving 254 U.g−1, or an enzyme activity per area of 2.8 U.m−2; such value was higher than the one obtained when the commercial matrix Octadecyl Sepabeads was used (328 U.g−1, 2.4 U.m−2). Such results point out that there is an optimum concentration of GMA epoxide groups that should be incorporated into the supports. The greater enzymatic activity obtained for 25% of GMA nanobiocatalyst was achieved not only because of their textural properties, but also due to a favorable interaction between the epoxide groups and CAL B. These results highlight the potential use of the heterofunctional matrices for the synthesis of new market‐competitive biocatalysts.