This study investigates the role of WhatsApp Commerce—the use of WhatsApp for business transactions—in empowering women-led Micro, Small, and Medium Enterprises (MSMEs) in Tier-3 cities of India, while advancing Sustainable Development Goals (SDGs) 5 (Gender Equality) and 8 (Economic Growth). Despite India’s digital revolution, gender disparities persist, with women leading only 20% of MSMEs and facing barriers like digital exclusion and sociocultural constraints. Grounded in Kabeer’s Empowerment Theory and Davis’s Technology Acceptance Model, the research employs a mixed-methods approach, combining surveys of 400 women entrepreneurs and 20 case studies across four Tier-3 cities (Bareilly, Jalgaon, Dibrugarh, Erode). Key findings reveal that WhatsApp usage intensity correlates with a 27% revenue increase (β = 0.27, *p* < 0.01), while UPI adoption boosts revenues by 19%. Digital literacy emerges as the strongest predictor of success (β = 0.42, *p* < 0.001), mediating 39% of WhatsApp’s impact on operational autonomy. Regional disparities are evident, with Erode’s textile sector outperforming others (71% autonomy, 42% revenue growth) due to collective bargaining via WhatsApp groups. However, older women (≥35) face 2.1× more male interference in digital transactions, highlighting sociocultural trade-offs. The study contributes to ICT4D literature by framing WhatsApp as hybrid digital infrastructure and proposes policy measures, including sector-specific digital literacy programs and women-only UPI IDs, to foster gender-inclusive ecosystems. By bridging grassroots digital commerce with SDG frameworks, this research offers actionable insights for policymakers to leverage informal platforms for equitable economic participation in emerging economies.