This paper deals with the investigation of the possibilities to improve the innovation performance in Bulgarian biotechnology firms. The main research purpose is to analyze Bulgaria's position concerning the innovative development of bio-based production. Methodological tools of the research methods were processing quantitative data, content analysis, and comparative situational analysis in combination with dynamic graphic analysis. The results of the research showed that there is a significant deficit in Bulgaria in the innovative development of biotechnology firms. The enhancement of the innovative biotechnological state of Bulgarian firms is a matter of great importance to their successful production and market performance on both the local and international markets. A small number of firms manage to find an adequate solution to creating stable market advantages and face insurmountable difficulties in trying to make it on the global market. Furthermore, Bulgaria's membership in the EU creates additional formal demands for providing a high quality of the production process, putting the local biotechnology firms in an even more challenging position. It suggests that companies need to focus their attention on producing goods with high added value (which is the basis of innovation) and applying and perfecting successful market-oriented approaches. In that relation, the arguments were summarized for the practical benefits of designing a complete model focused on biotechnology firms' market orientation, which is of crucial importance for their long-term innovative development. The study presents an author's conceptual model for measuring innovation performance of biotechnology firms which contains three constructs: market orientation, knowledge integration orientation, R&D effectiveness. The results from the conducted research could be helpful to research and practice R&D developers of firms with an established presence and long market history and upstart enterprises that cannot rely on income from their market activity, market or production experience.