Objective: While improving health literacy can enhance health among older adults, surmountable barriers preclude full utilization. The purpose of this study was to prospectively measure health literacy changes in older adults with chronic conditions exposed to home monitoring-based telenursing (HMBTN) by examining its link with their experiences of HMBTN, self-care, symptoms, and health status. Methods: In this study, a prospective fully longitudinal mixed methods design was employed. Eighteen older adults with chronic conditions, such as diabetes, congestive heart failure, chronic obstructive pulmonary disease, amyotrophic lateral sclerosis, and non-small cell lung cancer were included in a 12-week HMBTN intervention. Health literacy, self-care, and symptoms were assessed quantitatively, interviews were conducted to understand experiences with HMBTN, and healthcare/telenursing care records were reviewed to collect health status at baseline, mid-term, and after HMBTN. The findings were converged twice to facilitate the drawing of interpretations and super-meta-inferences throughout the study. Results: Sixteen participants completed the 12-week HMBTN intervention program. Their scores for applying (p = .031) and understanding health literacy (p =.039), and self-care activities (p =.002) significantly improved. Qualitatively, their ambivalent feelings about and expectations for HMBTN at baseline changed as they made positive lifestyle adjustments through usage. Increased motivation, sense of confidence, and better understanding of symptoms involving self-management were linked to improvements in health literacy. Conclusions: Improvements in the applying and understanding domains of health literacy among older adults with chronic conditions were linked to their proficiency in utilizing new technologies to make appropriate lifestyle changes. Furthermore, they developed a sense of confidence through their daily HMBTN.