Background <p><i>Houttuynia cordata</i> (<i>H. cordata</i>) is an important plant used for both medicinal and edible purposes. However, the metabolic profile and biosynthetic pathways of its flavonoids are still poorly understood. Therefore, metabolomics and transcriptomics were employed to analyze the roots, stems, and leaves of <i>H. cordata</i>, aiming to clarify this issue.</p> Results <p>A total of 471 metabolites were identified, with flavonoids being the predominant class. Key flavonoids, including quercetin, kaempferol, and rutin, showed the highest relative abundance in leaves, subsequently confirmed by targeted absolute quantification. Transcriptomic analysis revealed a large number of differentially expressed genes (DEGs) among tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the phenylpropanoid and flavonoid biosynthesis pathways were significantly enriched among the DEGs. The majority of DEGs within these pathways, such as those encoding <i>PAL</i>, <i>4CL</i>, <i>CHS</i>, and <i>CHI</i>, were found to be up-regulated in the leaves. These genes were further validated by real-time quantitative PCR (RT-qPCR), which showed consistent results with the transcriptomic data.</p> Conclusions <p>This work provides a comprehensive overview of the metabolite distribution and gene expression in different parts of <i>H. cordata</i>. Our findings highlight the leaf as the primary site for flavonoid accumulation and biosynthesis in <i>H. cordata</i>, laying the foundation for the utilization of candidate genes and future functional characterization of these pathways.</p>