In the past few decades, dental implants have proven aesthetic outcomes to gain recognition as the best treatment options for replacing missing or failing teeth with the optimal partnership of the patient and the Prosthodontist/Implantologist/ Restorative Dentistry Specialist. Polymicrobial biofilm formation on titanium surfaces becomes the main risk factor for inflammatory processes on tissues surrounding implant devices coupled with bone loss, which leads to implant failure. In an era of evidence-based dental medicine, considering the past and present medical histories of the patient to rule out possible elevated risk implant failure becomes a cause for concern. Periodontitis and peri-implantitis are polymicrobial infectious diseases on one hand. On the other hand, both have hyper-immune responsiveness from the host. There is no consistency in the finding of peri-implantitis-associated microbiome due to methodological variations in metagenomic studies conducted to this date. Moreover, there is controversy over the difference in microbiome profiles among periimplantitis and periodontitis. Putative periodontal pathogens seem to flourish in peri-implants-affected sites, suggesting the increasing virulence of those oral pathogens in dysbiosis and immunosuppressive conditions. Peri-implantitis biomaterial biofilm-associated polymicrobial infection called peri-implantitis could be among the root causes of dental implant failure with remaining unresolved issues and intrigue intricacies. Against this backdrop, this opinion aims to provide novel insights into the potential of dental implantology to unravel the mysteries in microbiology of peri-implantitis with a view to resolving the problem, though the work is still in its infancy. A lot more rigorous research is warranted in this regard, not only to define the implant associated microbiome but also to find a trustworthy solution to biological implant failure at the dawn of antibiotic-coated biomaterial production.