Effective extrahepatic activity of therapeutic oligonucleotides remains an unresolved and significant problem in the development of new genetic medicines. Targeted delivery to the heart is of particular interest due to the unmet need to treat an increasing health burden of cardiovascular diseases and the identification of potential genetic therapeutic targets. Drawing inspiration from literature, we investigate the potential of tannic acid (TA) modifications to improve the activity of a model siRNA sequence in the heart. We developed the synthesis of a series of conjugates containing 1-3 (TA) units to study how molecularly defined numbers of TA ligands influence activity. While we observe significant knockdown of the siRNA target gene in the liver, we did not in the heart, suggesting that although TA ligands confer improved function of siRNA in the liver, extrahepatic activity was not enhanced. In addition, hetero-bifunctional siRNA conjugates containing both TA and albumin binding motifs were designed and their synergistic effects explored. Similarly, data suggests that TA ligands do not increase cardiac activity of siRNA in this context; however, we can conclude that both C16 and AlbuTag ligands do significantly improve siRNA activity in the heart. We believe this work provides important bioconjugation insight for polyphenolic molecules, like tannic acid, as well as the synthesis of hetero-bifunctional siRNA conjugates generally. Moreover, our findings will inform the design of novel targeting ligands and nanomaterials, especially for molecules that may possess emergent properties when present in high multiplicity compared to their monomeric forms.