A dissertation submitted in partial fulfilment of the requirements for Masters of Science in Accounting and Finance (MSc A & F) of Mzumbe University.This study examines the determinants of commercial bank‟s profitability in Tanzania. These determinants have been categorized into internal factors which are bankspecific characteristics and external factors which can further be divided into macroeconomic factors and financial structure factors. The main objective of the study is to determine the factors that influence commercial banks profitability in Tanzania and to make recommendations for management decision making and policy objectives. A panel data of commercial banks in Tanzania was analyzed taking into consideration of 4 Banks listed in DSE. Two key measures of profitability (dependent variables) were taken into consideration, but the purpose of making a regression analysis and analyze the relationship between the parameters, the researcher analyzed only ROA in his study. Bank-specific factors, which were incorporated, were capital adequacy, deposits, liquidity, asset quality, loans and advances. In addition, macroeconomic factors and financial structure factors including inflation, GDP, money supply and banking industry concentration. The results for the ROA model indicate that loans and advances to total deposits, customer deposits to total assets (liquidity) are positively significant to bank profitability while shareholders equity to total assets are negatively significant to bank profitability. Moreover, inflation and GDP were positively significant to bank profitability. Also, highly capitalized banks were seen to be more profitable compare to less capitalized one. The study recommended on reduction of expenses, Government policies on employment and investments should be intensified to increase the profitability, Efficient and effective liquidity management should be adopted and there should be a set of direction guideline to manage properly banks specific determinants. The study made a researcher to learn that financial performance performed by banks plays a significant role in assuring and maintaining stability of the countries‟ economic systems.