Multiphase systems are important in minerals processing, and usually include solid-solid and solid-fluid systems. Examples of operations in multiphase systems include flotation, dewatering, and magnetic separation, among several other unit operations. In this paper, the current trends in the process system engineering tasks of modeling, design, and optimization, in multiphase systems, are analyzed. Different scales of size and time are included, and therefore the analysis includes modeling at the molecular level and unit operation level, and the application of optimization for the design of a plant. New strategies for the modeling and optimization of multiphase systems are also included, with a strong focus on the application of artificial intelligence (AI) and the combination of experimentation and modeling with response surface methodology (RSM). The paper finishes with tools to study the uncertainty, both epistemic and stochastic, which is present in all mineral processing operations. It is shown that all these areas are very active and can help to understand, operate, design, and optimize mineral processing that involves multiphase systems.