Vitamin E is a dietary supplement synthesized only by photosynthetic organisms and, hence, is an essential vitamin for human well-being. Because of the ever-increasing demand for natural vitamin E and limitations in existing synthesis modes, attempts to improve its yield using plant in vitro cultures have gained traction in recent years. With inflating industrial production costs, integrative approaches to conventional bioprocess optimization is the need of the hour for multifold vitamin E productivity enhancement. In this review, we briefly discuss the structure, isomers, and important metabolic routes of biosynthesis for vitamin E in plants. We then emphasize its vital role in human health and its industrial applications and highlight the market demand and supply. We illustrate the advantages of in vitro plant cell/tissue culture cultivation as an alternative to current commercial production platforms for natural vitamin E. We touch upon the conventional vitamin E metabolic pathway engineering strategies, such as single/multigene overexpression and chloroplast engineering. We highlight the recent progress in plant systems biology to rationally identify metabolic bottlenecks and knockout targets in the vitamin E biosynthetic pathway. We then discuss bioprocess optimization strategies for sustainable vitamin E production, including media/process optimization, precursor/elicitor addition, and scale-up to bioreactors. We culminate the review with a short discussion on kinetic modeling to predict vitamin E production in plant cell cultures and suggestions on sustainable green extraction methods of vitamin E for reduced environmental impact. This review will be of interest to a wider research fraternity, including those from industry and academia working in the field of plant cell biology, plant biotechnology, and bioprocess engineering for phytochemical enhancement.