Profitability is a key indicator for measuring the performance and sustainability of Islamic banks. This study aims to analyze the effect of Cost-to-Income Ratio and Non-Performing Financing on profitability (Return on Equity) with Financing to Deposit Ratio as an intervening variable. This research is quantitative research with a causal associative approach on Islamic Commercial Banks (BUS) registered with the Financial Services Authority (OJK) for the period 2019-2024. The sampling technique used was purposive sampling, resulting in a sample of 8 Islamic Commercial Banks. The data used is secondary data in the form of published annual financial reports. The data analysis techniques used were panel data regression testing and path analysis, using Eviews 12 software. The results of the study indicate that the Cost to Income Ratio does not affect profitability, Non-Performing Financing has a negative effect on profitability, the Cost to Income Ratio does not affect the Financing to Deposit Ratio, Non-Performing Financing has a positive effect on the Financing to Deposit Ratio, and the Financing to Deposit Ratio has a positive effect on profitability. Based on the results of the mediation test using the Sobel test, it was found that the Financing to Deposit Ratio was unable to mediate the effect of the Cost to Income Ratio on profitability. However, the Financing to Deposit Ratio was proven to be able to mediate the effect of Non-Performing Financing on profitability.