Tomatoes (Solanum lycopersicum L.) are among the most valuable vegetables worldwide. This appreciation is associated with their wide varieties and unique organoleptic characteristics. The industrial processing of tomatoes generates massive amounts of by-products, mainly used in the formulation of livestock feeding material or disposed of without further valorization. The by-products include peels, seeds, stems and cores, pomace, and juice residues, and they have been reported to be used in animal feed, fertilizers, dietary supplements, and food additives. Tomato by-products contain beneficial compounds such as carotenoids (lycopene, α-, β-, γ-, and ξ-carotenes, phytoene, phytofluene, and neurosporene), flavonoids (lutein), polyphenols, sterols, terpenes, and tocopherols, which have been reported to be used in the treatment of heart disease, inflammation, and certain cancers. By transforming tomato by-products into valuable materials, we can reduce the environmental impact of waste and contribute to developing a more sustainable tomato industry. This chapter will provide insights into the latest literature on tomatoes’ by-products, phytochemical contents, biological properties, and potential applications.