(1) Background: Peri-implantitis is a multi-factorial disease with an inflammatory background that occurs in both soft and hard tissues surrounding implants. In recent years, the understanding of the cellular, molecular and genetic background of peri-implantitis has broadened. This study aims to summarize the currently available articles on the subject and highlight the most recent advances over the last 20 years. (2) Methods: For this study, the Embase and PubMed libraries were searched using the keywords: (“peri-implantitis” AND “cytokine” OR “genetics” OR “cellular”) and (“peri-implantitis” AND “cytokine” OR “genetics” OR “cellular” AND “risk factors”). The search revealed a total of 3013 articles (992 from PubMed, 2021 from Embase). Following screening of the titles and abstracts and full-text reads, 55 articles were included. (3) Results: In peri-implantitis IL-6, IL-1β, TNF-α, MMP-8 and their genetic variations appear to be the most important cytokines in relation to not only pathogenesis, but also their potential diagnostic capabilities. Epithelial and inflammatory cells, along with those of the bone lineage, are prime cellular elements found in peri-implantitis. (4) Conclusions: A wide array of cells stand behind peri-implantitis, as well as cytokines and their genetic variations that take part in the process. However, the growing interest in this topic has led to the introduction of specific new diagnostic tools to enable a better understanding of patients’ responses to treatment and, in turn, to even enable prediction of the risk of developing peri-implant disease.