The perfusion-based in vitro three-dimensional (3D) tumor models built on the microfluidic technology are leading the current research in tumor modeling for testing anticancer drugs/agents. The conventional two-dimensional in vitro and animal models used in preclinical drug development have many drawbacks. Tumor models based on the microfluidic principles and technology promise to overcome many of those drawbacks. The inclusion of physiological tumor parameters on a microscale chip is beneficial in obtaining precise tumor pathology and meaningful drug responses, which can aid in predicting human clinical drug outcomes. In this chapter, we mainly focus on the microphysiological models, which have a flow component in the device design, and their maturation toward highly complex multiorgan systems. The microfluidic tumor models incorporating pharmacokinetics and pharmacodynamics (PK/PD) of anticancer drugs are explained. Finally, we discuss the challenges involved in the determination of drug absorption, distribution, metabolism, excretion, and toxicity, along with the recently developed 3D microfluidic tumor models that can help acquire these data as per the mathematical PK/PD models. © 2020 Elsevier Inc. All rights reserved.