Pear decline (PD), associated with ‘Candidatus Phytoplasma pyri’, is a major disease of pear in Europe and the United States. Several psyllid species are involved in the tritrophic system of PD as vectors of phytoplasmas belonging to the 16SrX group. Four years after the first detection of PD in Sicily, an integrated approach was applied to investigate the epidemic in a major pear-growing area. Visual surveys and molecular analyses were conducted over two years in eight orchards. A total of 115 plant samples and 101 Cacopsylla spp. specimens selected from a total of 1,435 collected individuals were analysed, confirming ‘Ca. P. pyri’ in 69% of symptomatic plants and in 4.6% of C. pyri individuals. Multilocus sequence typing (MLST) revealed high genetic similarity among 16SrX isolates. Remote sensing analyses since 2018, combined with vector monitoring, confirmed the epidemic nature of PD and the persistence of a risk of further pathogen spread within the region, proving, inter alia, to be a valid method for identifying the syndrome even on a large scale.