Histone deacetylases, often known as HDACs, are a class of enzymes that remove acetyl from the ε-N-acetyl lysine histones, thereby enabling histones to surround DNA with greater fidelity. HDACs are involved in a wide variety of biological activities, including gene regulation, transcription, cell proliferation, angiogenesis, migration, differentiation, and metastasis, among others. As a consequence, HDACs constitute an outstanding target for the discovery of anti-cancer drugs. The search for histone deacetylase inhibitors (HDACIs) has been expanded over the past decade with several B, and some have been offered. However, the HDACIs that are currently accessible are predominantly non-isoform selective and suffer from a number of problems, including limited efficacy, drug resistance, and toxicities. As a result, isoform-selective HDACIs and HDACIs with dual targeting capabilities have garnered a lot of attention from both academia and industry over the past five years. As a result, significant progress has been made in this field. In this paper, we summarize recent developments on HDACIs with dual targeting capabilities and their potential application in cancer treatment.