This original research article presents an empirical analysis of key business challenges in Eswatini from 2010 to 2025, interrogating them through a critical gendered lens. It addresses a significant gap in context-specific, gender-disaggregated data on the obstacles entrepreneurs face within the kingdom’s unique socio-economic landscape. Employing a sequential mixed-methods design, the study first analysed quantitative survey data from 350 micro, small, and medium enterprise owners. This was complemented by 25 in-depth qualitative interviews conducted between 2022 and 2024 to elucidate the survey findings. The results reveal a pronounced gendered divergence in both the perception and experience of core business constraints. While access to finance was a universal concern, women entrepreneurs disproportionately identified restrictive collateral requirements, discriminatory lending practices, and limited networking capital as systemic barriers. Furthermore, women emphasised socio-cultural expectations and unequal domestic responsibilities as significant, yet often unacknowledged, impediments to business growth; these challenges were less frequently cited by their male counterparts. The study contends that mainstream business support frameworks in Eswatini, and by extension in similar African contexts, remain gender-blind, thereby perpetuating inequality. The research underscores the imperative for policymakers and development agencies to design and implement gender-responsive interventions that address these deeply embedded structural and cultural constraints to foster inclusive economic development.