In this study, physical and functional properties of the cement composites containing ZnO, ZnO/lignin and lignin admixtures were investigated using Response Surface Methodology (RSM). The I-optimal design based on RSM was used to assess the influence of ZnO-based doping agent, of either commercial or synthetic origin, on cement composite production in the function of average compressive strength and cost. Polynomial mathematical models were developed by RSM confronting results from the experimental design. The accuracy and precision of the utilized models established by I¬-optimal design were tested using Analysis of Variance (ANOVA). The first stage of formulation optimization revealed that the use of commercially available ZnO-based admixture no. 4 (ZnO-SA, supplied by Sigma Aldrich) allowed to achieve the desired results, passing all the requirements, i.e., the best microbial purity combined with reasonable cost, followed by satisfactory physical properties. In the second stage of formulation optimization, the influence of implementing the hybrid materials, i.e., ZnO-SA mixed in different proportions with lignin was evaluated. RSM revealed that doping admixture no. 3, i.e., ZnO-SA/lignin (5:1), is the best candidate, which comprised augmented functional and physical properties of the fabricated cement composite. This component exhibited the best microbial purity as well as the lowest total pore volume, followed by satisfactory physical properties. Verification of the model findings indicated considerable agreement between the predicted and experimental values. From the findings, it was confirmed that a reasonable cost-performance balance for cement composites can be achieved using ZnO-SA and ZnO-SA/lignin (5:1).