The term SME encompasses a broad spectrum of definitions. Different organizations and countries set their own guidelines for defining small and medium enterprises. But the most important is that SMEs are the backbone of the national economy and the basis of the free enterprise economy. Considering the previous studies conducted on SMEs in Albania, it stressed the importance that they have on the economic growth of the country and the general level of the employment. The paper presents the model with the macroeconomic factors affecting the profit of SMEs in Albania, which includes the macroeconomic indicators such as GDP, the total number of active small and medium enterprises, CPI, Exports volume, Imports volume, the unemployment rate, the employment rate, and the exchange rate of Lek/Eur. But first, the paper analyzes the performance of the indicators in Albania during the last ten years and also makes a descriptive comparison between each of them and the SME profit (or profitability in some cases). Most of the macroeconomic factors we have selected were found not to be statistically significant and had no strong correlation with the firm’s profit. The number of the active SMEs, imports volume and exchange rate has the greatest impact on the profit.