Phytoplasmas can negatively or positively alter vector host fitness. “Candidatus Phytoplasma pyri,” is the causal agent of pear decline in commercial pear (Pyrus communis L.; Rosales: Rosaceae) and peach yellow leafroll in peach [Prunus persica (L.); Rosaceae]. This plant pathogen is transmitted by several species of pear psyllids (Cacopsylla spp. Hemiptera: Psyllidae). We sought to explore the relationship between the pear decline phytoplasma and its US vector, Cacopsylla pyricola (Förster), at the molecular genetic level through transcriptomic analysis using RNA-sequencing methodology. We also focused on phytoplasma and insect effectors, which are secreted proteins that can modulate interactions within a pathosystem. In this study, we identified 30 differentially expressed genes, 14 candidate insect effector genes, and 8 Ca. Phytoplasma pyri candidate effectors. Two strains of Ca. Phytoplasma pyri were identified based on immunodominant membrane protein sequence analysis from C. pyricola collected in the Pacific Northwest agricultural region. Here, we present a first genetic look at the pear decline pathosystem and report gene candidates for further exploration of infection mechanisms and potential tools for integrated pest management.