Background: Chronic diseases are putting huge pressure on health care systems. Nurses are widely recognized as one of the competent health care providers who offer comprehensive care to patients during rehabilitation after hospitalization. In recent years, telerehabilitation has opened a new pathway for nurses to manage chronic diseases at a distance; however, it remains unclear which chronic disease patients benefit the most from this innovative delivery mode., Objective: This study aims to summarize current components of community-based, nurse-led telerehabilitation programs using the chronic care model; evaluate the effectiveness of nurse-led telerehabilitation programs compared with traditional face-to-face rehabilitation programs; and compare the effects of telerehabilitation on patients with different chronic diseases., Methods: A systematic review and meta-analysis were performed using 6 databases for articles published from 2015 to 2021. Studies comparing the effectiveness of telehealth rehabilitation with face-to-face rehabilitation for people with hypertension, cardiac diseases, chronic respiratory diseases, diabetes, cancer, or stroke were included. Quality of life was the primary outcome. Secondary outcomes included physical indicators, self-care, psychological impacts, and health-resource use. The revised Cochrane risk of bias tool for randomized trials was employed to assess the methodological quality of the included studies. A meta-analysis was conducted using a random-effects model and illustrated with forest plots., Results: A total of 26 studies were included in the meta-analysis. Telephone follow-ups were the most commonly used telerehabilitation delivery approach. Chronic care model components, such as nurses-patient communication, self-management support, and regular follow-up, were involved in all telerehabilitation programs. Compared with traditional face-to-face rehabilitation groups, statistically significant improvements in quality of life (cardiac diseases: standard mean difference [SMD] 0.45; 95% CI 0.09 to 0.81; P=.01; heterogeneity: X 2 1 =1.9; I 2 =48%; P=.16; chronic respiratory diseases: SMD 0.18; 95% CI 0.05 to 0.31; P=.007; heterogeneity: X 2 2 =1.7; I 2 =0%; P=.43) and self-care (cardiac diseases: MD 5.49; 95% CI 2.95 to 8.03; P<.001; heterogeneity: X 2 5 =6.5; I 2 =23%; P=.26; diabetes: SMD 1.20; 95% CI 0.55 to 1.84; P<.001; heterogeneity: X 2 4 =46.3; I 2 =91%; P<.001) were observed in the groups that used telerehabilitation. For patients with any of the 6 targeted chronic diseases, those with hypertension and diabetes experienced significant improvements in their blood pressure (systolic blood pressure: MD 10.48; 95% CI 2.68 to 18.28; P=.008; heterogeneity: X 2 1 =2.2; I 2 =54%; P=0.14; diastolic blood pressure: MD 1.52; 95% CI -10.08 to 13.11, P=.80; heterogeneity: X 2 1=11.5; I 2 =91%; P<.001), and hemoglobin A1c (MD 0.19; 95% CI -0.19 to 0.57 P=.32; heterogeneity: X 2 4 =12.4; I 2 =68%; P=.01) levels. Despite these positive findings, telerehabilitation was found to have no statistically significant effect on improving patients' anxiety level, depression level, or hospital admission rate., Conclusions: This review showed that telerehabilitation programs could be beneficial to patients with chronic disease in the community. However, better designed nurse-led telerehabilitation programs are needed, such as those involving the transfer of nurse-patient clinical data. The heterogeneity between studies was moderate to high. Future research could integrate the chronic care model with telerehabilitation to maximize its benefits for community-dwelling patients with chronic diseases., Trial Registration: International Prospective Register of Systematic Reviews CRD42022324676; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324676., (©Athena Yin Lam Lee, Arkers Kwan Ching Wong, Tommy Tsz Man Hung, Jing Yan, Shulan Yang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 02.11.2022.)