Interest in hot-melt extrusion (HME) technology for novel applications is growing day by day, which is evident from several hundred publications within the last 5 years. HME is a cost-effective, solvent free, 'green' technology utilized for various formulations with low investment costs compared to conventional technologies. HME has also earned the attention of the pharmaceutical industry by the transformation of this technology for application in continuous manufacturing.Part II of the review focuses on various novel opportunities or innovations of HME such as multiple component systems (co-crystals, co-amorphous systems and salts), twin-screw granulation, semi-solids, co-extrusion, abuse deterrent formulations, solid self-emulsifying drug delivery systems, chronotherapeutic drug delivery systems, and miscellaneous applications.HME is being investigated as an alternative technology for preparation of multicomponent systems such as co-crystals and co-amorphous techniques. Twin-screw granulation has gained increased interest in preparation of granules via twin-screw melt granulation or twin-screw granulation. This novel application of the HME process provides a promising alternate approach in the formulation of granules and solid dosage forms. However, this technology may need to be further investigated for scalability aspects of these novel applications for industrial production.