The Indian commercial banking has witnessed various changes such as fraud cases, demonetization and sector sustainability during the study period year from 2009 - 2018, The paper focuses on to analyze affecting key drivers of Indian commercial banks bottom line. A sample of 30 banks was included, and ROA, R.O.E. and NIM were adopted as proxy variables to estimate profitability. The balanced panel data regression model was applied to achieve the desired objective. The research outcomes depict the liquidity and asset management positively impacted both ROA and R.O.E., whereas, G.D.P., operational efficiency and demonetization negatively impacted ROA and R.O.E. As per NIM is concerned, inflation rate, asset management, capital adequacy ratio and asset quality have a substantially positive impact, and significant negative impact variables are G.D.P., deposit and operational efficiency. The implication aspect is that banks should focus on liquidity and deposits for proper utilization and better performance. When a bank has more credits than debit, it depicts higher yield assets which produce more profitability. This results in an adverse relation between banks profitability and liquidity, which is required in our study. For improving the profitability policymakers and regulators should consider macroeconomic factors. © 2020 by Advance Scientific Research. This is an open-access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)