<p>Multi-material 3D printing (MM3DP) has emerged as a transformative advancement in additive manufacturing, enabling the fabrication of complex geometries with varied material properties, functionality, and mechanical performance. Unlike traditional single-material printing, MM3DP allows the integration of different material phases, including polymers, metals, ceramics, and composites, to create components with enhanced durability, conductivity, flexibility, and thermal resistance. This capability has led to significant advancements in industries such as aerospace, biomedical engineering, automotive manufacturing, and robotics, where customized material distributions are crucial. Among the various techniques of additive manufacturing, material extrusion (MEX)-based multi-material printing is gaining increasing attention due to its cost-effectiveness, accessibility, and adaptability in processing diverse material combinations. Emerging technologies in multi-nozzle deposition, single-nozzle material switching, and in situ material mixing have expanded the possibilities of fabricating functionally graded materials (FGMs) and hybrid composites. However, challenges such as material compatibility, bonding strength, post-processing constraints, and the need for real-time process optimization remain major barriers to widespread adoption. This review provides a comprehensive analysis of the latest developments in multi-material 3D printing, highlighting the role of computational simulations, optimization algorithms, and artificial intelligence (AI) in advancing process efficiency. Furthermore, the paper discusses emerging applications, recent innovations in material formulation, and future directions, emphasizing the need for cost-effective, sustainable, and scalable solutions for industrial adoption. Through this holistic review, we aim to provide valuable insights into the current state of MM3DP, its technological frontiers, and the ongoing efforts to overcome its limitations in diverse applications.</p>