The alloys required for fossil fuel power systems are transitioning from stainless steels that operate below 600oC to nickel-based alloys that can operate up to 760oC in advanced ultra-super critical steam turbines. This transition brings with it major metallurgical as well as economic challenges related to alloy design, melt processing, and fabrication of these large size components. The alloys, in general, must maintain creep resistance over 100,000 hours of service life while at the same time maintaining resistance to severe steam oxidation and general oxidation. A need exists for nickel-based alloys that are not only highly alloyed, but are also impervious to phase instabilities during initial processing and service. The potential exists for severe segregation when casting large ingots. This possibility must be dealt with during thermo-mechanical processing to obtain the wrought structures that can be inspected to design defect levels. This paper will detail these challenges as they have been addressed in smaller aerospace turbines and discuss strategies to overcome these problems. New computational modeling tools will play a critical role in engineering solutions for alloy design, solidification, forging, and heat treatment. Since any solution also needs to be economically viable, the paper also discusses processing cost issues in terms of the process yields and operational strategies. The use of powder metallurgy will also be reviewed as a cost effective alternative to alloys that have traditionally been cast-wrought processed.