The aim of this umbrella review is to evaluate what are the most common medications and systemic diseases that can affect bone–implant integration, the success rate and survival rate of dental implants, peri-implant tissue health, and implant loss. Systematic reviews, with meta-analysis or not, about how systemic diseases and medications influence dental implant osseointegration, survival rate, success rate, and peri-implant diseases, published only in the English language, are electronically searched across the most important scientific databases. The present umbrella review includes eight systematic reviews, and osteoporosis and diabetes are the most investigated pathologies. Systemic diseases, such as neurologic disorders, HIV, hypothyroidism, cardiovascular diseases, and drugs, such as beta blockers, anti-hypertensives, or diuretics do not show a decreased rate of implant osseointegration. It seems that drugs, such as proton-pump inhibitors (PPIs) or serotonin reuptake inhibitors (SSRIs), negatively affect implant osseointegration. Few studies compare the effects of drugs and systemic diseases on the parameters considered in this overview. It is important to underline how the results of this review need to be validated with subsequent and more reviews.