Pertussis, caused by Bordetella pertussis, remains a public health concern despite long-standing vaccination programs. After a marked decline during the COVID-19 pandemic, a resurgence was observed in Europe and Italy, with a sharp increase in 2024. This study describes pertussis epidemiological trends in the Tuscany Region (Italy) from 2019 to 2024 to identify high-risk groups and inform prevention strategies. A retrospective population-based analysis was conducted using cases reported to the national surveillance system (PREMAL). Incidence rates were calculated using ISTAT population data, and demographic, temporal, and clinical characteristics were analyzed. Overall, 669 cases were reported (mean annual incidence rate: 3.03/100,000 (IC 95% 2.47–3.59; period incidence rate: 18.2/100,000 (IC 95% 16.81–19.56)), with 89% occurring in 2024 (16.34/100,000 (IC 95% 15.03–17.65)). No sex differences were observed, and most cases were reported in Central Tuscany (64%). Children under 15 years accounted for 87% of cases. The highest incidence was observed among 10–14-year-olds, while infants < 1 year, particularly those under 4 months, showed the highest burden in narrower age strata. Hospitalizations occurred in 12.6% of cases, decreasing substantially in 2024. The 2024 resurgence likely reflects waning immunity, disruptions to routine vaccinations during the pandemic, and reduced pathogen circulation in previous years due to containment and isolation measures related to the pandemic. Strengthening surveillance and improving booster and maternal vaccination coverage are essential to protect vulnerable populations.