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Endoplasmic reticulum (ER) is one of the most important sub‐cellular organelles which controls myriads of biological functions including protein biosynthesis with proper functional folded form, protein misfolding, protein transport into Golgi body for secretion, Ca2+ homeostasis and so on. Subsequently, dysregulation in ER function leads to ER stress followed by disease pathology like cancer. Hence, targeting ER in the cancer cells emerged as one of the futuristic strategies for cancer treatment. However, the major challenge is to selectively and specifically target ER in the sub‐cellular milieu in the cancer tissues, due to the lack of ER targeting chemical moieties to recognize the ER markers. To address this, in the last decade, numerous biomaterials were explored to selectively impair and image ER in cancer cells to induce ER stress. This review outlines those biomaterials which consists of carbon and silicon materials, lipid nanoparticles (liposomes and micelles), supramolecular self‐assembled nanostructures, cell membrane‐coated nanoparticles and metallic nanoparticles. Moreover, we also discuss the challenges and possible solutions of this promising field to usher the readers towards next‐generation ER targeted cancer therapy. [ABSTRACT FROM AUTHOR]