India’s rapidly growing automobile industry has intensified the need for sustainable fuel alternatives to reduce dependency on imported fossil fuels and mitigate greenhouse gas (GHG) emissions. This study examines the potential of second-generation biorefineries as a comprehensive solution for efficient biomass valorization in India. With a projected bioethanol demand of 10,160 million liters by 2025 for India’s 20% ethanol blending target, there is an urgent need to develop sustainable production pathways. The biorefinery approach enables simultaneous production of multiple valuable products, including bioethanol, biochemicals, and bioproducts, from the same feedstock, thereby enhancing economic viability through additional revenue streams while minimizing waste. This paper systematically analyzes available biomass resources across India, evaluates integrated conversion technologies (biochemical, thermochemical, and synergistic approaches), and examines current policy frameworks supporting biorefinery implementation. Our findings reveal that second-generation biorefineries can significantly contribute to reducing GHG emissions by up to 2.7% of gross domestic product (GDP) by 2030 while creating rural employment opportunities and strengthening energy security. However, challenges in supply chain logistics, technological optimization, and policy harmonization continue to hinder large-scale commercialization. The paper concludes by proposing strategic interventions to overcome these barriers and accelerate the transition toward a sustainable circular bioeconomy in India.