This study gave an evaluation of the relationship between entrepreneurial orientation and cultural values on performance of small and medium-sized enterprises (SMEs) in southwest Nigeria. Primary method of data collection was used. Data were collected through the use of structured questionnaire administered randomly on carefully selected sample of 400 owners, managers/supervisors of SMEs who have been in existence for a period of a minimum of five years and above through multi-stage sampling technique. Structural equation modelling (SEM) was used to examine the relationship between entrepreneurial orientation and cultural values on the performance of SMEs in southwest Nigeria. The result indicates that both entrepreneurial orientation and cultural values are strongly related with high level of relationship. This study concluded that managers need to leverage the dimensions of both entrepreneurial orientation such as innovativeness, proactiveness, and risk taking as well as the dimensions of cultural values such as individualism/collectivism, power distance, masculinity/femininity, uncertainty avoidance to achieve optimal business performance. Keywords: Entrepreneurial orientation, small and medium-sized enterprises, performance, dimensions. cultural values