Background/Objectives: To elucidate how flower retention regulates leaf quality formation in Dendrobium officinale and to provide a theoretical basis for high-quality leaf cultivation and high-value utilization of byproducts, D. officinale leaves were subjected to two treatments: flower retention (FR) and flower removal (FT). Methods: Quantitative analysis revealed significant differences in quality-related compounds between the two treatments. Specifically, the polysaccharide content in the FR group (8.72%) was significantly lower than that in the FT group (9.37%). Conversely, the FT group exhibited a significantly higher total flavonoid content (1.74%) compared to the FR group (1.41%). Additionally, the total phenol content in the FR group (0.90%) was significantly higher than that in the FT group (0.69%) (n = 3). Results: Compared with the FR group, the FT group exhibited significantly higher levels of total flavonoids, polysaccharides, tyrosine (Tyr), hydroxylysine (Hylys), lysine (Lys), histidine (His), and arginine (Arg). A total of 1999 (39.5%) of the 5062 annotated metabolites were accumulated significantly differently. The FT group was mainly characterized by upregulated secondary metabolites, including flavonoids. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that nucleotide metabolism, purine metabolism, aminoacyl-tRNA biosynthesis, and flavonoid biosynthesis were the core differential pathways. Furthermore, the differential metabolites exhibited a metabolic trade-off of “upregulated secondary metabolism and downregulated primary metabolism”. Conclusions: Our findings indicated that flower removal can significantly increase the active flavonoid components and amino acids in D. officinale leaves and optimize the quality of this medicinal leaf by regulating the source–sink relationship, carbon–nitrogen partitioning, and key metabolic pathways.