Using the GMM estimator, this paper empirically studies the bank-specific, industry specific and macroeconomics specific determinants of bank profitability of 259 commercial banks in the South Asian countries (Bangladesh, India, Nepal and Pakistan) for the period of 1997-2012. Empirical results show a low level of profit persistency and a late-hit of the global financial crisis in the banking sector in the region. We found no evidence for the traditional SCP hypothesis in relation to banking profit but financial solvency and managerial excellence have positive affiliation. Cost of fund, liquidity, funding gap, term structure of interest rate and economic growth rate found negative influence while rate of inflation positively affect bank profit. Also to report that South Asian banks are operating with ‘inefficient’ manpower.