Background: Identifying patients with a strong pro-inflammatory phenotype may allow clinicians to underpin high-risk individuals based on early inflammatory marker profiles and to personalize approaches to preventative treatments. Aim: The objective of this systematic review is to synthesize the results of previous studies on osseointegration to show which pro-inflammatory cytokines and chemokines have been detected and quantified during the initial phase of osseointegration. Material and methods: PubMed, Embase, Scopus, ISI Web of Science, and Cochrane Library were searched for articles published until August 2024. A descriptive summary was produced to explain study variations, including patients’ characteristics and results. The methodological quality of each included study was assessed based on Downs and Black’s checklist. Results: 30 studies were selected for inclusion. In total, 710 patients received 1329 implants (an average of 1.87 implants per participant). A total of 32 biomarkers were analyzed. The overall trend observed in levels of pro-inflammatory cytokines and chemokines appears to be an early peak, followed by a progressive reduction in levels throughout the observation periods. Conclusions: The available evidence suggests that a strong expression of pro-inflammatory biomarkers is a feature of osseointegration, and an over- or underexpression of certain biomarkers could have an effect on early marginal bone levels. Several of these markers are mechanistically implicated with implant pathology; however, the prognostic value of early cytokine expression and correlation with long-term clinical outcomes requires further research.