(1) Understanding the effects of manufacturing factors on microbial adhesion is essential for optimizing additive denture base materials and improving their clinical performance. This study evaluated how polymerization time, layer thickness, extended cleaning, and storage conditions influence C. albicans and S. mutans adhesion on a denture base material. (2) Specimens (n = 15/group, d = 8 mm, h = 2 mm) were additively fabricated or poured (reference). Digital light processing was performed with varying polymerization times, layer thicknesses, extended cleaning, and storage. Microbial adhesion was assessed using a luminescence assay. Surface properties were characterized by roughness (Sa/Sz), hardness, and surface free energy (SFE). Statistics: The Shapiro–Wilk test, ANOVA, Bonferroni post hoc test, and Pearson correlation (α = 0.05) were utilized. (3) Polymerization time, layer thickness, cleaning, and storage conditions significantly influenced C. albicans and S. mutans adhesion. Increased layer thickness reduced C. albicans adhesion but promoted S. mutans colonization, emphasizing the role of SFE. Extended polymerization and optimized cleaning reduced microbial adhesion, highlighting the need for tailored processing to enhance microbial resistance and material integrity. (4) Manufacturing factors influenced microbial adhesion, with additive materials reducing the abundance of C. albicans but increasing the abundance of S. mutans, underscoring the importance of material adjustments and extended polymerization to enhance microbial resistance.