Enzymatic depolymerization of postconsumer polyurethanes (PURs) offers a promising route for sustainable plastic waste management. However, the complex chemistry of PURs containing carbamate, ether, and ester bonds poses a challenge for such a biotechnological process. Here, we explored the deconstruction of a commercial polyether-polyester-PUR through a cascade depolymerization approach, in which a low-temperature thermal pretreatment (180°C, 4 h) was combined with tandem enzymatic hydrolysis. Heat treatment modified the polymer's physicochemical properties, enabling the cutinase HiC from Humicola insolens to cause more than 8% weight loss of the treated PUR films, versus less than 2% of the untreated control after 48 h incubation. Furthermore, the addition of the metagenomic urethanase SP2 completed the one-pot enzymatic cascade, achieving not only depolymerization to the constituent monomer, 4,4′-methylenedianiline (MDA), but also a nearly 3-fold increase in MDA yield compared to using SP2 alone. Docking studies highlighted HiC's specificity toward ester bonds in the PUR polymeric units, and two HiC variants further enhanced degradation within 24 h. Altogether, this work lays the foundation for future investigation and process design for the depolymerization of polyether-polyester-PURs and related materials by cascade enzymatic reactions.