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Background In 2016, Nepal adopted the World Health Organization's Package of Essential Non-Communicable Disease Interventions (PEN) to address the rising burden of non-communicable diseases (NCDs). This study evaluated the primary healthcare system's readiness to prevent and manage major NCDs, including cardiovascular diseases (CVDs), diabetes mellitus (DM), and chronic respiratory diseases (CRDs), and associated factors. Methodology: We conducted a convergent parallel mixed-methods study between 2020 and 2022. We assessed 105 primary healthcare facilities selected through multistage stratified random sampling. Data were collected using the WHO Service Availability and Readiness Assessment (WHO-SARA) tool and analyzed using survey-weighted descriptive and multivariable linear regression. Simultaneously, we conducted qualitative interviews with 23 health authorities and 47 health service providers involved in PEN implementation. Interview transcripts were thematically analyzed using WHO-SARA domains. Results NCD service readiness was highest for CVDs (48.4, 95% CI: 44.5-52.3), followed by DM (40.8, 95% CI: 36.1-45.5), and CRDs (34.8, 95% CI: 30.8-38.9). Primary Healthcare Centers (PHCCs), primary healthcare facilities in hilly regions, or those charging user fees, demonstrated higher NCD service readiness than health posts, mountain-region primary healthcare facilities, and those without user fees. Qualitative findings associated higher NCD service readiness with better infrastructure, medical supplies, training opportunities, and social health insurance. High staff turnover and limited medical supplies hindered NCD service delivery, particularly in health posts and remote regions. Conclusion Primary healthcare facilities in Nepal lack equipment, medicines, trained staff, and NCD guidelines. The government could enhance NCD service readiness by building capacity and improving the availability of medical supplies.