(1) Background: Lotus (Nelumbo nucifera Gaertn.) is an aquatic plant with a long history and ornamental, edible, medicinal, and commercial value. All parts of the lotus are important “homologous and different effects” medicinal herbs as distinct parts of the same plant with different medicinal effects. (2) Methods: Six representative medicinal parts of lotus were selected, i.e., the lotus flower (Nelumbinis Flos, Flo), lotus petiole (Nelumbinis Petiolus, Pet), lotus seedpod (Nelumbinis Receptaculum, Rec), lotus stamen (Nelumbinis Stamen, Sta), lotus seed (Nelumbinis Semen, Sem), and lotus plumule (Nelumbinis Plumula, Plu), and analyzed via UPLC-MS/MS for metabolite profiling and RNA sequencing for gene expression. Weighted gene co-expression network analysis identified several transcription factor families related to flavonoid synthesis. (3) Results: Distinct metabolite accumulation and gene expression patterns were observed, particularly in the flavonoid synthesis pathway. Key findings included important metabolic profiles in stamens, high flavonoid content in light-exposed tissues, and functional differentiation in seeds and plumules. The discovered transcription factor families are essential for flavonoid biosynthesis and contribute to molecular breeding and resource utilization. (4) Conclusion: This study provides an important theoretical basis for molecular breeding of lotus, quality control of medicinal materials, and the rational use of resources obtained from different medicinal parts of lotus.

(1) Background: Lotus (Nelumbo nucifera Gaertn.) is an aquatic plant with a long history, with ornamental, edible, medicinal, and commercial value. All parts of lotus are important “homologous and different effects” medicinal herbs as distinct parts of the same plant with different medicinal effects. (2) Methods: Six representative medicinal parts of lotus were selected, i.e., lotus flower (Nelumbinis Flos, Flo), lotus petiolous (Nelumbinis Petiolus, Pet), lotus seedpod (Nelumbinis Receptaculum, Rec), lotus stamen (Nelumbinis Stamen, Sta), lotus seed (Nelumbinis Semen, Sem), and lotus plumule (Nelumbinis Plumula, Plu). Analyzed via UPLC-MS/MS for metabolite profiling and RNA sequencing for gene expression. Weighted gene co-expression network analysis identified several transcription factor families related to flavonoid synthesis. (3) Results: Distinct metabolite accumulation and gene expression patterns were observed, particularly in the flavonoid synthesis pathway. Key findings included important metabolic profiles in stamens, high flavonoid content in light-exposed tissues, and functional differentiation in seeds and plumules. The discovered transcription factor families are essential for flavonoid biosynthesis and contribute to molecular breeding and resource utilization. (4) Conclusion: This study provides an important theoretical basis for molecular breeding of lotus, quality control of medicinal materials, and the rational use of resources obtained from different medicinal parts of lotus.