<i>Background</i>: The pharmaceutical and related commodities manufacturing industry in Ethiopia is long-lived because the country is well-endowed with basic raw materials and local ownership and to some extent with machinery and technological know-how. The pharmaceutical industry, both globally and in Africa, encounters challenges in internationalizing products. In Ethiopia, challenges like regulatory complexities and limited government support hinder international market access for pharmaceutical products. This aim is to explore the barriers and understand why Ethiopian pharmaceuticals struggle to enter global markets. <i>Method</i>: The study adopted a mixed research approach, integrating qualitative and quantitative methods. It focuses on 15 pharmaceutical industries in Ethiopia, particularly those in Addis Ababa and the Oromia Special Zone, using probability and none probability sampling technique. The total study participants involved in the quantitative and qualitative studies were 373 and 15, respectively. Data collection comprises questionnaires, key informant interviews, and observation checklists, supplemented by secondary data from official and theoretical sources. Ethical considerations underscore obtaining verbal consent and ensuring confidentiality. Analysis entails descriptive statistics and qualitative synthesis, with numerical analysis conducted using STATA 14.1 software. <i>Results</i>: Out of the expected 384 study participants, 373 (97.13%) participated in our study, while the entire group of participants proposed in the qualitative study (15) also participated in this study. Key findings include resource constraints, regulatory issues, and biased perceptions against local products, hindering their global recognition. While strong political commitment and effective policy enforcement at the top government level are crucial, inadequate collaboration across government tiers undermines these efforts. Despite existing policies, inadequate implementation and procedural guidance diminish industry interest. There's uncertainty about government support for local pharmaceutical production, with persistent challenges like resource shortages and policy inconsistencies impeding progress. Perceptions vary on the effectiveness of policies promoting local production, and concerns about taxation issues impact the industry. Nevertheless, most respondents’ express confidence in the quality of domestically produced pharmaceuticals. <i>Conclusion</i>: Despite crucial government commitment, weak collaboration across levels impedes progress. Respondents note deficient policy implementation and doubt government support. Persistent issues like resource shortages persist, along with taxation concerns, despite locally produced products being perceived as equal in quality. To advance, better policy implementation, regulatory harmony, financial support, infrastructure enhancement, increased awareness, and improved collaboration are essential.