The citrus mealybug, Planococcus citri (Risso) (Hemiptera: Pseudococcidae), is a major insect pest of greenhouse-grown horticultural crops. Applications of systemic insecticides as drenches to the growing medium are typically used by greenhouse producers to prevent or suppress citrus mealybug populations. A comprehensive study was conducted that included 11 experimental trials designed to assess the effects of growing medium applications of six systemic insecticides (azadirachtin, dinotefuran, flonicamid, imidacloprid, spirotetramat, and thiamethoxam) in preventing the establishment of and suppressing citrus mealybug populations on different plant species. The experimental trials included four plant species: Solenostemon scutellarioides, Gerbera jamesonii, Begonia × semperflorens-cultorum, and Salvia splendens, with six different cultivars grown in research greenhouses similar to those used in greenhouse production systems. In addition, feeding location (plant stem, leaf top, and leaf bottom) of citrus mealybugs on the various plants was also recorded. Overall, percent citrus mealybug mortality was consistently <50% (n = 255 to 1,598) for any treatment or rate of application; regardless if the systemic insecticides were applied preventatively or curatively. Percent citrus mealybug mortality did reach 78% (n = 36) for thiamethoxam at 8 times the label rate when plants were treated preventatively. Furthermore, none of the treatments prevented development of citrus mealybug F₁ individuals to F₂ generation egg-laying females on S. scutellarioides or G. jamesonii plants. Citrus mealybugs varied in their spatial distribution on the plant stem, leaf top, and leaf bottom with no noticeable trends. Therefore, based on the results of the study, systemic insecticides are not effective against the citrus mealybug in greenhouse production systems.