This study investigates the synthesis and characterization of composite biofilms obtained from the whole plum oil cake (POC), focusing on the effects of process parameters on film properties. Glycerol concentration (10%, 15%, and 20%); pH (8, 10, and 12); and temperature (60 °C and 90 °C) were selected as variables due to their significant influence on the mechanical, physico-chemical, barrier, and structural properties of the biopolymer films. The 55% of synthesized films were coherent and selected for further analysis. The results showed satisfactory elongation at break values (up to 47.39%), but low tensile strength values (0.97 to 8.87 MPa). The film’s water content (9.43 to 22.16%) and solubility (36.12 to 74.21%) values were primarily influenced by glycerol content and pH, while swelling (58.98 to 100.42%) was mainly dependent on glycerol and temperature. Low water vapor transmission rate (WVTR) values (1.45 to 4.88 g/m2h) demonstrated great potential for food packaging application. All samples exhibited UV barrier properties, indicating them for light-sensitive foods packaging. Fourier transform infrared spectroscopy (FTIR) analysis showed that process parameters affected the structure of the films and confirmed the existence of macromolecules in the plum oil cake films, originating from POC chemical composition. Optimization of the ANN model for multivariable parameters was achieved using obtained activation functions and weight coefficients and biases showing that POC film synthesized with 20% glycerol, at pH 12 and temperature 60 °C exhibited optimal properties. The optimal process parameters identified in this study support the potential use of POC in developing edible films for food packaging. This approach reduces pollution from conventional plastics by offering biodegradable alternatives. The valorization of agricultural waste and reduced exploitation of non-renewable resources align with key circular economy principles.