The current study is analyzing various factors that determine the profitability of a bank. More importantly, this article has tried to evaluate the relationship between bank-specific and macroeconomic variables with banks profitability. To quantify the profitability of the banking industry of Bangladesh, Return on Equity (ROE) and Return on Assets (ROA) are used as dominated variables. Independent variables are IRS, CAR, NIITA, CR, LTD, DG, SIZE, GDP, INF and NETWORK. Relevant data comes from 30 Bangladeshi commercial banks. Panel data regression result describes Capital Adequacy Ratio (CAR), Total Assets (SIZE) and Inflation (INF) has a positive association with bank profitability in Bangladesh. Credit Risk (CR) has the highest influences on the dependent variables and Non-interest Income to Total Assets (NIITA) has the lowest. The study provides guidelines to the goal setters of financial institutions. It provides a direction for the governing body to formulate and improve relevant policies and the outcomes suggest that banks should manage credit risk and utilize deposits in more productive segments of the economy of the country to ensure sustainable benefits.