The primary aim of this study is to analyze the factors that influence the profitability of commercial banks in Nepal between the years 2011/2012 and 2020/2021 A.D., with a focus on bank-specific determinants. The study utilizes a random sampling method to select a sample of 16 commercial banks, and the profitability of these banks is measured using the dependent variable, return on assets (ROA). Similarly, the study explores the relationship between ROA and six independent variables: capital adequacy ratio, asset quality, bank liquidity, bank size, interest spread, and deposit growth. Descriptive and causal comparative research designs were used and employed panel data regression analysis to investigate the impact of the independent variables on ROA. Random effect model was taken as fitted model after the model diagnosis using Eviews-12 computer software. The results reveal that capital adequacy ratio and interest spread have a positive and significant impact on ROA. In contrast, deposit growth has a negative and significant effect on ROA. However, the study does not find any significant relationship between bank liquidity, bank size and assets quality and ROA. Overall, the study suggests that banks in Nepal should focus on improving their capital adequacy ratio and interest spread to enhance their profitability. Additionally, they should carefully manage their deposit growth to avoid negative effects on profitability.