This review focuses on the current disparities and gaps in research on the characteristics of the oral ecosystem of denture wearers, making a unique contribution to the literature on this topic. We aimed to synthesize the literature on the state of current knowledge concerning the biological behavior of the different polymers used in prosthetics. Whichever polymer is used in the composition of the prosthetic base (poly methyl methacrylate acrylic (PMMA), polyamide (PA), or polyether ether ketone (PEEK)), the simple presence of a removable prosthesis in the oral cavity can disturb the balance of the oral microbiota. This phenomenon is aggravated by poor oral hygiene, resulting in an increased microbial load coupled with the reduced salivation that is associated with older patients. In 15–70% of patients, this imbalance leads to the appearance of inflammation under the prosthesis (denture stomatitis, DS). DS is dependent on the equilibrium—as well as on the reciprocal, fragile, and constantly dynamic conditions—between the host and the microbiome in the oral cavity. Several local and general parameters contribute to this balance. Locally, the formation of microbial plaque on dentures (DMP) depends on the phenomena of adhesion, aggregation, and accumulation of microorganisms. To limit DMP, apart from oral and lifestyle hygiene, the prosthesis must be polished and regularly immersed in a disinfectant bath. It can also be covered with an insulating coating. In the long term, relining and maintenance of the prosthesis must also be established to control microbial proliferation. On the other hand, several general conditions specific to the host (aging; heredity; allergies; diseases such as diabetes mellitus or cardiovascular, respiratory, or digestive diseases; and immunodeficiencies) can make the management of DS difficult. Thus, the second part of this review addresses the complexity of the management of DMP depending on the polymer used. The methodology followed in this review comprised the formulation of a search strategy, definition of the inclusion and exclusion criteria, and selection of studies for analysis. The PubMed database was searched independently for pertinent studies. A total of 213 titles were retrieved from the electronic databases, and after applying the exclusion criteria, we selected 84 articles on the possible microbial interactions between the prosthesis and the oral environment, with a particular emphasis on Candida albicans.