Background: Study aim was to investigate the vaccination status against vaccine-preventable diseases (VPD) of frail adults during the SARS-CoV-2 pandemic and, for those subjects eligible for at least one vaccine, with respect to the recommended vaccination in line with the Italian National Vaccination Prevention Plane (NPVP), to explore the willingness to be vaccinated. Methods: A cross-sectional study was carried out among adults aged ≥ 60, immunocompromised or subjects affected by chronic conditions. Results: Among the 427 participants, a vaccination coverage rate lower than the targets for all the vaccines considered was found. Of those, 72.6% of subjects stated their willingness to receive recommended vaccinations, and 75.2% of the respondents stated that the advice to undergo vaccinations was received by the General Practitioner (GP). In a multivariable logistic regression model, higher odds of recommended VPD vaccination uptake (defined as having two or more of the recommended vaccinations) were associated with the willingness towards recommended VPD vaccination (Odds Ratio = 3.55, 95% Confidence Interval: 1.39 to 9.07), university education (OR = 2.03, 95% CI: 1.03 to 3.97), but having another person in the household (OR = 0.52, 95% CI: 0.28 to 0.97), and history of oncological disease (OR = 0.39, 95% CI: 0.18 to 0.87) were predictive of lower odds of vaccination uptake. In another multivariable model, higher odds of willingness to receive vaccines were associated with kidney disease (OR = 3.3, 95% CI: 1.01 to 10.5), perceived risk of VPD (OR = 1.9, 95% CI: 1.02 to 3.3), previous influenza vaccination (OR = 3.4, 95% CI: 1.8 to 6.5), and previous pneumococcal vaccination (OR = 3.1, 95% CI: 1.3 to 7.7), but increasing age (OR = 0.93 per year, 95% CI: 0.91 to 0.97), working (OR = 0.40, 95% CI: 0.20 to 0.78), and fear of vaccine side effects (OR = 0.38, 95% CI: 0.21 to 0.68) were predictive of lower odds of willingness to receive vaccines. Conclusions: Despite specific recommendations, vaccination coverage rates are far below international targets for frail subjects. Reducing missed opportunities for vaccination could be a useful strategy to increase vaccination coverage in frail patients during the routine checks performed by GPs and specialists.