Although existing research identifies different profiles of vaccine-hesitant individuals, most studies focus on isolated psychological constructs, neglecting their interplay in shaping vaccination attitudes. Using data from an online survey of a representative sample of Italian adults, we examined vaccination attitudes through a person-centered methodology. We selected personal values, attitudes, and beliefs for their potential relevance to vaccination attitudes and conducted an exploratory factor analysis to reveal the latent relationships among these variables. This approach allowed us to identify four underlying psychological drivers: Eco-humanism (altruistic/biospheric values and connectedness to nature), Skeptical Perspective (distrust in science, conspiracy mentality, and spirituality), Goal-Driven Positive Mindset (hope and optimism), and Self-Centered Attitude (hedonic/egoistic values). We then assessed how adherence to each driver related to vaccination attitudes, as measured by the VAX-I scale, using multiple linear and quantile regression models. Results showed that higher adherence to Eco-humanism resulted in more positive vaccination attitudes, particularly lower mistrust in vaccine benefits and reduced concerns about pharmaceutical companies’ profiteering. In contrast, a stronger alignment with the Skeptical Perspective was linked to more negative attitudes, including increased mistrust in vaccine benefits, heightened concerns about vaccine safety and pharmaceutical companies’ profiteering, and a greater preference for natural immunity. Likewise, higher adherence to Self-Centered Attitude was tied to an overall more negative stance, particularly marked by amplified worries about unforeseen long-term effects, heightened concerns about pharmaceutical companies’ profiteering, and an increased preference for natural immunity. Goal-Driven Positive Mindset, although not significantly associated with overall vaccination attitudes, was inversely related to mistrust in vaccine benefits. These findings suggest that vaccination attitudes are shaped by distinct psychological profiles, supporting the development of tailored, human-centered vaccine promotion strategies.