Red-leaf lettuces, rich in bioactive compounds like anthocyanins and flavonoids, offer health benefits by reducing oxidative stress and boosting immunity. This article provides an extensive review of the genetic, epigenetic, environmental, and technological factors influencing anthocyanin biosynthesis and leaf coloration in red-leaf lettuce, emphasizing its significance in agriculture and nutrition. The genetics of anthocyanin biosynthesis, environmental influences, practical applications, agronomic insights, and future directions are the main areas covered. Anthocyanin accumulation is regulated by structural, regulatory, and transporter genes, as well as the MYB-bHLH-WD40 (MBW) complex. Mutations in these genes impact coloration and stress responses. Advances in genomic studies, such as GWAS and QTL mapping, have identified key genes and pathways involved in anthocyanin biosynthesis, aiding breeding programs for desirable traits. In addition, light intensity, stress conditions (e.g., drought, temperature), and phytohormones affect anthocyanin levels and photomorphogenesis in general. Controlled environments, like vertical farms, optimize these conditions to enhance pigmentation and phytochemical content. LED lighting and tailored cultivation techniques improve color intensity, antioxidant capacity, and yield in controlled settings. Sustainable production technologies for red-leaf lettuce in vertical farms are being developed to meet consumer demand and promote functional foods, integrating genetic, epigenetic, and environmental research into agronomy. This review highlights red-leaf lettuce's aesthetic, nutritional, and functional value, advocating for innovative cultivation methods to enhance its market and health potential.