Machining of nickel-based superalloys still poses several problems, especially slot milling, because the high work hardening, high metal carbide content and poor thermal conductivity cause the tool to wear quickly, with frequent breakages. This paper has dealt with the investigation of the effects of flood cooling, cryogenic cooling with Liquid Carbon Dioxide (LCO2), and the Minimum Quantity Lubrication and LCO2 combination on the cutting force, tool wear, chip morphology, surface roughness and the width of the milled slots. The authors have developed a new measurement method to measure the edge radius wear as a function of the depth of cut. The importance of this measurement method lies in the fact that at each measurement level, it is possible to determine the degree of wear of each edge radius and the homogeneity of the wear of the tool edges, which allows for determining how close the tool is to failure. Initially, the cooling had a positive effect on the cutting force for both LCO2 and LCO2 + MQL, but towards the end of the machining length, the cutting force was lower for flood cooling. The smallest tool wear resulted from the flood cooling, followed by LCO2 + MQL combination and LCO2. These results suggest that lubricating is more important than cooling for tool life. However, cooling plays a major role in chip breakage and surface quality, and in both cases, the best results were obtained by milling with the LCO2 + MQL combination.