Surgery, chemotherapy, radiotherapy, and hormone therapy are the main common anti-tumor therapeutic approaches. However, the non-specific targeting of cancer cells has made these approaches non-effective in the significant number of patients. Non-specific targeting of malignant cells also makes indispensable the application of the higher doses of drugs to reach the tumor region. Therefore, there are two main barriers in the way to reach the tumor area with maximum efficacy. The first, inhibition of drug delivery to healthy non-cancer cells and the second, the direct conduction of drugs into tumor site. Nanoparticles (NPs) are the new identified tools by which we can deliver drugs into tumor cells with minimum drug leakage into normal cells. Conjugation of NPs with ligands of cancer specific tumor biomarkers is a potent therapeutic approach to treat cancer diseases with the high efficacy. It has been shown that conjugation of nanocarriers with molecules such as antibodies and their variable fragments, peptides, nucleic aptamers, vitamins, and carbohydrates can lead to effective targeted drug delivery to cancer cells and thereby cancer attenuation. In this review, we will discuss on the efficacy of the different targeting approaches used for targeted drug delivery to malignant cells by NPs.