The aim of the research is to find out the relationship between the internal and external factors that affect the profitability of a bank. For this, a panel data of five years from 2005 to 2009 has been taken on quarterly basis for 11 banks in Pakistan. This paper uses regression analysis to implicate the results with the hypotheses. The factors taken into consideration are Bank size, Advances (Loans), Deposits (Liability), Non- interest income, Credit Risk, Interest income, Expense Management, Discounted rate, Imports, Exports and CPI. The result from the analysis shows that, few of internal variables have significant influence on a bank’s profitability whereas external variables do not affect profitability of the banks.