Background <p>The prevalence of chronic diseases and chronic comorbidities among the older adults is increasing annually with the advent of an aging population, making health management for older patients with chronic conditions essential. However, optimizing management models requires mobilizing the patients’ own agency. Individual capacity, specifically self-efficacy and health literacy, plays a pivotal role in this process. Therefore, this study aims to analyze the relationship between self-efficacy, health literacy, and health status among older patients with comorbidities, and further explore the potential pathways by which self-efficacy and health literacy are associated with health status. The goal is to provide a scientific basis for informing the refinement of comorbidity management models for older adults and supporting better health status of patients.</p> Methods <p>Adopting a multistage stratified cluster random sampling method, older patients with multimorbidity in communities of Shenzhen, Guangdong Province were selected as the survey subjects. Using the “Health Survey Questionnaire for older patients with multimorbidity” for face-to-face interviews, 1200 older adults were surveyed, and 987 valid patient data were selected. Descriptive analysis was conducted on the self-efficacy, health literacy, and health status of older patients with multimorbidity in Shenzhen, Guangdong Province. A structural equation model was constructed to analyze the mediating effect of health literacy between self-efficacy and health status.</p> Results <p>In the survey of 987 older patients with multimorbidity in this study, the average score for self-efficacy was 8.07 ± 1.36, indicating a high level on average; the average score for health literacy was 32.16 ± 9.39, suggesting a possible inadequacy in health literacy level; and the average score for health status was 73.60 ± 19.70. The well-fitted structural equation model results demonstrate that self-efficacy (<i>β</i> = 0.148, <i>P</i> &lt; 0.001) and health literacy (<i>β</i> = 0.317, <i>P</i> &lt; 0.001) of older patients with multimorbidity are positively associated with health status. Specifically, the mediating effect of health literacy on the relationship between self-efficacy and health status accounts for 38.1% of the total effect (Effect size = 0.042, 95% <i>CI</i>: 0.022–0.069), serving as a partial mediator with a significant mediating effect.</p> Conclusions <p>In the multimorbidity management model for older adults, interventions such as patient peer support groups and case manager-led health education are proposed as theoretical strategies. These potential measures aim to support patient self-efficacy and facilitate health literacy, thereby potentially contributing to better overall health of patients.</p>