This research aims to develop microphysiological models for studying pathophysiology across multiple organ types with an emphasis on cancer. The primary design considerations are to enable the culturing of multiple tissue/organ types and establish fluidic interconnectivity to facilitate chemical communication between them. Engineering individual organ compartments with relevant physiological functions is a basic requirement for multiorgan models. However, to fully capture organism physiology, a multi-organ model must allow transport to occur through a living vascular endothelium. This thesis presents the engineering and validation of two separate multi-organ devices platforms. The first device features a multilayer configuration that uses membranes to separate channels and compartments. The multilayer device is a simple implementation that achieves the goal of intercellular communication between organ compartments. The second device features a membrane-free design that enables cell transit between adjacent channels and chambers in a horizontal configuration. The membrane-free devices achieve the goal of enabling physiological (perfusable) vascularization in the system. A digital manufacturing-based workflow previously established in our lab enabled rapid prototyping and design iteration. Primary contributions of this thesis include optimizing the designs of these MPS models for future use by reaching almost 100% loading success rates and establishing standardized workflows for device fabrication that address inherent limitations of our equipment. Following the reduction to practice phase, both device platforms were used to establish a prototype MPS model of cancer cachexia, which is driven by tumor inflammation. This thesis work established tissue engineering methods for interfacing a lung cancer module with three placeholder stromal-vascular tissues. We used ICAM-1 as a marker of vascular inflammation and tested the hypotheses that cancer will induce vascular inflammation in the model and that the effect will be a function of distance from the tumor module in the device. This thesis establishes a foundation for more complex implementations with representative organ modules incorporated such as muscle, liver, and adipose tissue and complete vascularization.