Nuclear receptors (NRs) are transcription factors (TFs) involved in diverse biological activities, such as cell proliferation, embryogenesis, differentiation, homeostasis, metabolism, and immunity. The NR superfamily has been implicated in many pathologies such as cancer, cardiovascular disease, inflammation, and reproductive abnormalities. The expression of different NRs has been well explored in various cancers, and they have been shown to have oncogenic or tumor-suppressive functions. NRs associated with cancer include retinoic acid receptor (RAR), retinoid X receptor (RXR), peroxisome proliferator-activated receptor gamma (PPARγ), and vitamin D receptor (VDR). Due to their physiological activation via low-molecular-mass ligands, many NRs have been recognized as tractable small-molecule therapeutic targets through extensive studies.