Background: Suboptimal health is identified as a reversible phase occurring before chronic diseases manifest, emphasizing the significance of early detection and intervention in predictive, preventive, and personalized medicine (PPPM/3PM). While the biological and genetic factors associated with suboptimal health have received considerable attention, the influence of social determinants of health (SDH) remains relatively understudied. By comprehensively understanding the SDH influencing suboptimal health, healthcare providers can tailor interventions to address individual needs, improving health outcomes and facilitating the transition to optimal well-being. This study aimed to identify distinct profiles within SDH indicators and examine their association with suboptimal health status. Method: This cross-sectional study was conducted from June 16 to September 23, 2023, in five regions of China. Various SDH indicators, such as family health, economic status, eHealth literacy, mental disorder, social support, health behavior, and sleep quality, were examined in this study. Latent profile analysis was employed to identify distinct profiles based on these SDH indicators. Logistic regression analysis by profile was used to investigate the association between these profiles and suboptimal health status. Results: The analysis included 4918 individuals. Latent profile analysis revealed three distinct profiles (prevalence): the Adversely Burdened Vulnerability Group (37.6%), the Adversity-Driven Struggle Group (11.7%), and the Advantaged Resilience Group (50.7%). These profiles exhibited significant differences in suboptimal health status (p < 0.001). The Adversely Burdened Vulnerability Group had the highest risk of suboptimal health, followed by the Adversity-Driven Struggle Group, while the Advantaged Resilience Group had the lowest risk. Conclusions and relevance: Distinct profiles based on SDH indicators are associated with suboptimal health status. Healthcare providers should integrate SDH assessment into routine clinical practice to customize interventions and address specific needs. This study reveals that the group with the highest risk of suboptimal health stands out as the youngest among all the groups, underscoring the critical importance of early intervention and targeted prevention strategies within the framework of 3PM. Tailored interventions for the Adversely Burdened Vulnerability Group should focus on economic opportunities, healthcare access, healthy food options, and social support. Leveraging their higher eHealth literacy and resourcefulness, interventions empower the Adversity-Driven Struggle Group. By addressing healthcare utilization, substance use, and social support, targeted interventions effectively reduce suboptimal health risks and improve well-being in vulnerable populations.