This study investigated the intricate interplay between entrepreneurial orientation (EO) and firm performance within the context of the influencing role of religiosity. Entrepreneurial orientation has been extensively recognized as a key driver of small and medium-sized enterprise (SMEs) performance. However, the influence of religiosity on the relationship between entrepreneurial orientation and performance remains an understudied area. Hence, the study examined the effect of entrepreneurial orientation on the performance of Micro, Small, and Medium-sized Enterprises (SMEs and MSMEs) as well as the moderating role of religiosity on the entrepreneurial orientation and performance relationship. The descriptive survey research design was adopted while the population of the study was 9,730 registered MSMEs within the Sub-Urban areas of South-Eastern Nigeria. Three hundred and seventy (370) firms were drawn using the Krecjie and Morgan technique. Partial least square – structural equation modeling (PLSSEM) was used to test the study hypotheses. The decision rule for the hypotheses was set at a 0.05 significance level. The result showed statistically significant positive effects of risk taking on performance; and innovativeness on performance. In addition, religiosity had a significant moderating influence on entrepreneurial orientation and performance. Conclusively, the study posits that small businesses should have an entrepreneurial outlook to their operational activities if they would survive the challenges they face in uncertain and challenging environments like Nigeria, further stating that the adoption and practice of the religious tenets improve the wellbeing of entrepreneurial firms.