In Nigeria, there is gender discrimination in both social and cultural settings which hindered women regardless of their population, educational, economic and social status, a fair representation in policy making, business related matters and manpower development. A consequence of which has a severe negative impact on women entrepreneurship. Against this background, this paper examine the effect of socio-economic variables economic environment and gender differences in entrepreneurship and specifically investigate whether gender difference affects the rate of new business creation and investigate the effect of socio-economic factors on genders differences in entrepreneurship as well as the effect of economic environment on genders differences in entrepreneurship. The study utilized annual time series data sourced from the World Bank Development Index (WDI) covering the period of 2005 to 2016. In the estimation, as a preliminary test, the Jarque-Bera Normality test, line graph trend analysis, and unit root test conducted while the Dynamic Ordinary least squares (DOLS) cointegration approach as proposed by Stock and Watson (1993) was employed for the estimation of both the gender difference in entrepreneurship model and socio-economic and economic environment determinants of gender difference model. The result showed that there was no significant gender difference (= 0.372011, t=1.011480, p>0.05) in entrepreneurship in Nigeria. It was also found that gender differences (=-0.090982, t=-3.229165, p<0.05) and the level of economic development (=-0.154879, t=-2.973507, p<0.05) exerts a significant negative effect on entrepreneurship in Nigeria while education and income level do not showed any effect on entrepreneurship in Nigeria. In order to ensure equal participation of men and women in entrepreneurship, the level of income of the Nigerian populace should be enhance through expansionary fiscal policy by reducing taxes specifically personal income tax 4and raising productive government expenditure.