The persistent fight against global environmental threats and energy catastrophe is currently a major concern for the economic development of bioenergy across the entire country. Hence, traditional fuel-based reserves are overburdened to cope with the rapid energy crisis, necessitating an urgent need for an innovative carbon-neutral green-energy resource. In order to address these critical bottlenecks, microalgae with incredible metabolic versatility have paved the way for a pivotal attention towards sustainable biofuel production. However, due to high operational costs and low lipid productivity, the microalgae-based biofuel resource is still in its infancy. As a result, this problem can be overcome by incorporating engineered microalgal strains which can pave the way for significant lipid augmentation for biofuel production. Thus, our current review depicts an in-depth understanding of a multi-omics approach to microalgae, the broad scope of self-sustaining microalgae cultivation, lipid-extraction strategies, and conversion processes to improve economic commercialization in the bioenergy framework. The present review also provides a detailed analysis of the international and national status of bioenergy development by several federal agencies.