One of the most important instruments of the financial system that reveals the future of the economy in any country is the profitability of the banking sector. Starting from 2008, Egypt was banged by consecutive shocks, both globally and locally, started with global financial crisis in Sep., 2008. The essential objective of the current study is to investigate factors that affect Egyptian banks’ profitability before and after financial crisis using Generalized Method of Moments (GMM) through Eviews. The sample period covers from 2004 to 2013, return on assets and return on equity were used as proxy for banks’ profitability. The explanatory variables which affect profitability are deposits to total assets ratio, operating income to asset ratio, credit quality, capital adequacy, loans rate, equity growth minus loan growth rate, asset share ratio and Egyptian banks’ total assets to Egyptian gross domestic product (GDP).The empirical findings suggested that Egyptian banks with higher capital strength, asset share, and efficient management exhibit higher profitability level, whilst Egyptian banks with higher credit risk and loans intensity exhibit lower profitability level.