The Indian pharmaceutical industry has emerged as one of the most significant contributors to economic growth, attracting substantial foreign direct investment (FDI) while simultaneously supporting a large number of domestically owned firms. This study examines the Return on Investment (ROI) performance of FDI-based and non-FDI-based pharmaceutical companies operating in India. Using panel data techniques, including Fixed Effects and Random Effects models, the research investigates the influence of profitability, liquidity, leverage, and efficiency indicators on ROI. The findings reveal that the determinants of ROI differ across the two categories of firms. For FDI-based companies, efficient receivables management, represented by the debtor’s turnover ratio, significantly improves ROI, whereas traditional financial indicators show limited influence. In contrast, Return on Equity (ROE) emerges as the most important determinant of ROI among non-FDI companies. The comparative analysis further indicates that non-FDI firms report a higher average ROI than FDI firms. The study highlights the importance of firm-specific characteristics and demonstrates that the factors driving investment returns vary according to ownership structure. The findings provide valuable insights for investors, policymakers, and corporate managers seeking to enhance financial performance and investment efficiency in the Indian pharmaceutical sector.