<p>Nearly half of cancer survivors are nonadherent to oral anticancer medications (OAM), yet no studies have systematically examined health belief profiles or identified belief-based intervention targets to improve adherence and health-related quality of life (HRQoL). This study aimed to categorize distinct health belief profiles and examine their associations with medication adherence and HRQoL among cancer survivors. This cross-sectional online survey study recruited participants from two crowdsourcing panels across the U.S. between June and July 2024. Latent profile analysis was used to categorize participants’ patterns of health beliefs. Eligibilities were self-reported who had a cancer diagnosis and were currently taking at least one OAM. Participants completed a 54-item online survey assessing cancer perceptions, beliefs about OAMs, medication adherence and HRQoL. One-way analysis of variance (ANOVA) and multivariate regression analysis were conducted to compare group differences and examine the associations between health belief profiles, adherence and HRQoL. Among 323 respondents, three distinct health belief profiles emerged, significantly associated with adherence (adjusted <i>R</i>^<i>2</i> = 0.491, <i>F</i> change = 27.07, <i>p</i> &lt; 0.01) and HRQoL (adjusted <i>R</i>^<i>2</i> = 0.286, <i>F</i> change = 6.12, <i>p</i> &lt; 0.01). The <i>Optimistic and adaptive</i> profile (13.3%) demonstrated strong understanding of OAM use, greater perceived control over recurrence, fewer negative cancer consequences, and high perceived necessity with minimal concerns about medication. The <i>Conscious but hesitant</i> profile (30.7%) maintained balanced perceptions of cancer and treatment but reported the lowest perceived necessity for medication. The <i>Overwhelmed and unaware</i> profile, the largest subgroup (56.0%), exhibited greater perceived cancer consequences, higher treatment concerns, the lowest adherence and the lowest HRQoL. Subgroup analysis revealed that specific beliefs significantly associated with nonadherence (perceived risk of recurrence) and HRQoL (cancer and treatment consequences and emotional responses), suggesting that reframing negative beliefs may improve outcomes. To support sustained medication adherence and HRQoL, interventions should focus on enhancing patient education about the role of OAMs in cancer control, addressing concerns about side effects, and enhancing access to resources that alleviate cancer-related consequences. Future research should explore the mechanisms through which health beliefs affect adherence and identify unmet emotional and informational needs among cancer survivors.</p>