The preservation of marble heritage artifacts is increasingly challenged by microbial-induced chemical deterioration. Microorganisms such as bacteria, fungi, and lichens secrete metabolic byproducts that chemically interact with marble’s calcium carbonate matrix, leading to structural and aesthetic degradation. This paper reviews the mechanisms of microbial-induced chemical deterioration, discusses the impacts on marble artifacts, and evaluates current conservation strategies. Marble, a widely used material in cultural heritage monuments, is highly susceptible to biodeterioration caused by microbial colonization. This study investigates the chemical deterioration of marble heritage artifacts induced by microbial activity, focusing on the metabolic byproducts of bacteria, fungi, and lichens. Field sampling and laboratory analysis revealed that microbial communities secrete organic acids (oxalic, citric, and gluconic acids) and sulfur compounds, which react with calcium carbonate (CaCO3), leading to the formation of calcium oxalates and gypsum. These reactions significantly increased surface porosity, discoloration, and micro-cracking. Results demonstrated that oxalic acid–producing fungi were the most aggressive agents of marble degradation, with calcium oxalate crystals reducing the structural density of samples by up to 28% compared to unaffected controls. Biofilm formation was also observed, enhancing moisture retention and pollutant deposition, thereby accelerating deterioration. Conservation treatments with natural biocides (essential oil extracts) showed a reduction of microbial colonization by 65%, while protective hydrophobic coatings decreased surface porosity and acid infiltration. This research highlights the urgent need for eco-friendly conservation strategies tailored to microbial-induced damage, ensuring the long-term preservation of marble heritage artifacts.