Monolithic fuel is a candidate fuel form for the conversion of high-performance research reactors. This plate-type fuel consists of a high-density, U-Mo alloy-based fuel in a monolithic form that is sandwiched between zirconium diffusion barriers and encapsulated in an aluminum cladding. To qualify this fuel system, the program must demonstrate that the fuel meets the safety standards, has a predictable behavior, and performs well in a reactor. Although many plates have shown satisfactory thermo-mechanical performance in reactor, a small number of experimental plates exhibited failures, rendering performance of these plates unacceptable. Post-irradiation examinations of failed plates have revealed that various failures modes are present, including pillowing, blistering, buckling, warping, delamination, fracture, rupture, oxide spallation, etc. Previous studies have implied that such various operational and loading conditions could generate a complex stress-strain state, facilitating distinct failure modes that could impact the structural integrity. To understand such various failure modes, a comprehensive set of studies focusing on failure modes is being performed. As a part of these studies, this work studies the cladding-cladding separation failures that were observed in some of previous irradiation tests. To understand the root cause of cladding separation failures, selected plates from previous irradiation experiments were simulated under comparable operational conditions. Stress-strain state of the plates at the interface were examined. The results were comparatively evaluated to understand possible effects of stress state of the bond-line on delamination failures. This paper presents these findings, discusses such failure modes, and examines the influence of various factors on previously observed cladding delamination failures.