MXenes, including transition metal carbides, nitrides, and carbonitrides, are highly versatile materials because of their adjustable structure and rich surface chemistry. They are projected to compete with, and in some cases outperform, graphene as two dimensional (2D) substrate for a wide range of applications. MXenes are prone to self-restacking due to hydrogen bonding and/or van der Waals interactions, which can induce a significant loss of the electroactive area as well as ion and electrolyte inaccessibility. In this regard, hybridization or composite formation of 2D MXenes with low-dimensional nanostructures in intricately designed architectures provides an innovative chance to integrate their unique properties in a complementary way. The design of hybrid nanocomposites of 2D MXenes and 0D nanomaterials can effectively combine the advantages of both individual constituents (surface property tuning, small molecule attachments, external stimuli sensitivity, robust environmental resistance, negligible inferences to other analytes, and recyclability), synergistically overcoming their individual shortcomings. The purpose of this review is to highlight recent advancements in this novel area, with a focus on the design, methodologies, structural and functional synergies, and emerging applications, including next-generation smart electronics, futuristic devices, sensors, waste treatments, anti-biofouling, and point-of-care diagnostic platforms as well as the major challenges to be overcome in the future.