This paper investigates the waste heat recovery potential of internal combustion engines, using organic Rankine cycles running on small-scale radial turbomachinery. ORC are promising candidates for low-grade thermal sources and the use of dynamic expanders yields very compact systems, which is advantageous for automotive applications. As engine coolant and exhaust gases are the major available heat sources, different cycle configurations and working fluids have been investigated to capture them, in both urban and highway car operation. Pareto fronts showing the compromise between net power output and total heat exchange area have been identified for a set of cycle’s variables including turbine inlet conditions and heat exchanger pinches. A preliminary optimization, including only R-1234yf working fluid, shows that a single-source regenerative cycle harvesting the high temperature exhaust gas stream performs averagely better than coolant-driven and dual-source cycles. A more in-depth optimization including eight working fluids as well as aerodynamic and conceptual limitations related to radial turbomachinery and automotive design constraints, finally shows that an ICE exhaust heat recovery ORC could improve the first law efficiency of the driving system by up to 10% when implemented with fluid R-1233zd.