Breast cancer (BC) is recognized as the most typical cancer diagnosed in women globally, posing significant public health challenges. Several protein-based biological macromolecules have been investigated for drug delivery in BC treatment due to biological and tunable mechanical properties. Silk fibroin (SF)-based hydrogel/scaffold is gaining attraction in BC therapy. The functionalization of SF with folic acid or antibodies enables targeted delivery to BC cells that overexpress folate receptors. In this context, this perspective article explored the potential biological activity, targeting capacity, functionalization, and drug carrier abilities of SF-based hydrogel for BC therapy. In addition, the article exclusively delves into the potential molecular pathways of SF-based hydrogel/ scaffolds for targeted therapy in BC. The article also summarizes the perspectives on the diagnosis abilities of SF-based hydrogel/ scaffolds in BC treatment, making it the first instance of such perspective literature. This insightful literature presents practical guidance for researchers, clinicians, and scientists eager to investigate the innovative biological applications and targeting potential of SF-based hydrogels and scaffolds in advancing breast cancer treatments.