As the literature highlights, many health behavior theories try to explain both social and psychological variables influencing an individual’s health behavior. This study integrates insights relative to the antecedents of getting vaccinated from health behavior theories, particularly including the health belief model (HBM), the theory of planned behavior (TPB), and the different socio-demographic factors. Furthermore, we considered the possible mechanism of impact of distrust in science on individuals’ hesitance and resistance to taking up SARS-CoV-2 vaccination in subjects living in Italy. A correlational study of 1095 subjects enrolled when the national vaccination campaign for the third dose was launched. A questionnaire was used to measure: Italian Risk Perception; subjective norm; trust in science, trust in the vaccine; fear of COVID-19; fear of the vaccine; perceived knowledge about SARS-CoV-2; booster vaccination intention. Principal results show that: (i) the positive relationship provided by HBM theory between perceptions of SARS-CoV-2 risk (vulnerability and severity) and intention to have the vaccine, through fear of COVID-19; (ii) the positive relationship between subjective norms and both trust in science and vaccination intention; (iii) that trust in science plays a crucial role in predicting vaccination intention. Finally, the results provided indications about a positive relationship between subjective norms and fear of COVID-19, and a full mediation role of trust in science in the relationships between determinants of both TPA and HBM, fear of COVID-19, and vaccination intention. In conclusion, an individual’s intention (not) to get vaccinated requires the consideration of a plethora of socio-psychological factors. However, overall, trust in science appears to be a key determinant of vaccination intention. Additional strategies promoting healthy behavior are needed.