Background: There is an increasing burden of care for chronic noncommunicable diseases on the health care system, in particular, in mixed urban-rural districts where resource constraints and limited health workers threaten continuity of care. Nurse practitioners (NPs), who have received clinical training to assess, diagnose, and educate patients, are coming to play an increasingly important role in the care of people with chronic diseases. Thrown into the limelight of chronicity, NPs and their roles and practice barriers are less documented, at least in some Indian settings. Objectives: This study was to describe the extent of the NP practice in managing chronic disease and examine self-perceived competency across core clinical and educational domains, and activity options, in addition to exploring the regulatory, organizational, and interprofessional factors that make possible or hinder the NP effectiveness in Osmanabad district, Maharashtra. Methods: A descriptive cross-sectional survey was carried out among 80 conveniently selected NPs employed in primary and community health centres of Osmanabad. A self-assessment questionnaire was validated and used to assess five domains: clinical assessment, treatment and medication management, patient education and self-management support, care coordination, and system roles. The Likert-scale items were analysed using descriptive statistics (means, standard deviations, frequencies), and open-ended responses were subjected to thematic analysis between two independent researchers to identify the barriers and facilitators. Results: NPs performed history-taking (mean 4.6 ± 0.5) as well as initiating pharmacotherapy according to guidelines (4.4 ± 0.6) with high competence, indicating their good clinical basis. Adverse-event monitoring (3.9 ± 0.9) and telehealth follow-up (3.9 ± 0.9) scores were below average for continued education. A high degree of commitment to patient empowerment for self-management was indicated for patients' understanding of the disease process (4.5 ± 0.6) and for showing them how to perform self-monitoring (4.3 ± 0.7) (domains of patient education). Regulatory and restricted diagnostic authority and restricted diagnostic authority were primary barriers, and supportive interdisciplinary teams and access to decision-support tools were key facilitators, as revealed by thematic analysis. Conclusion: Nurse practitioners in Osmanabad are significant providers of care for chronic disease, but need further training in the management of adverse events and telehealth delivery. And so, policy reforms that are providing NPs with diagnostic and prescriptive autonomy, that are being combined with structured capacity-building interventions, will maximize the impact and influence of their contributions.