Global economy is driven by entrepreneurs operating micro, small, medium, and large-scale enterprises (M-SMLEs). This probe integrates three distinct domains, entrepreneurship, leadership, and gender, particularly women. In a previous study, one of the co-authors investigated such phenomenon that comprised motivations and pre-and-post venture challenges for women entrepreneurial leaders and devised a conceptual framework. This inquiry applies quantitative methods to empirically test and validate such framework, and contribute towards pertinent theoretical underpinning. It avails post-positivism philosophy, deductive approach, and survey method. Data was garnered from women entrepreneurial leaders of Pakistan – a growing emerging market of South Asia. The sample size includes 308 samples (comprising micro, small, and medium-scale enterprises (M-SMEs), 100+ participants from each category. The capabilities, circumstances, and behavior of M-SMEs differ than those of such leaders from large-scale enterprises; therefore, they were ignored purposefully. Structural Equation Modeling (SEM) technique was availed for data analysis. Canons of reliability, validity, and triangulation assisted toward robust results. The findings reveal that motivation to become entrepreneur and need of situation appeared the most significant predictors for starting and leading a venture by women. In challenges before the start of business (discouragement from family and gender stereotypes, financial challenges, lack of entrepreneurial knowledge, and lack of access to market and workplace [in a male-dominated society]) appeared significant predictors in order. And in challenges after the start of business (lack of market research, lack of finance and sustainability, harassment from men, and gender stereotypes from employees) respectively appeared significant predictors of women entrepreneurial leadership.