Manufacturing process routes of materials can be adapted to manipulate their microstructure and hence their tribological performance. As industrial demands push the applications of tribological materials to harsher environments of higher stress, starved lubrication, and improved life performance, manufacturing processes can be tailored to optimize their use in particular engineering applications. The aim of this paper was therefore to comprehend the structure-property relationships of a wear resistant cobalt-based alloy (Stellite 6) produced from two different processing routes of powder consolidated hot isostatic pressing (HIPing) and casting. This alloy had a nominal composition of Co–28Cr–4.5W–1C, which is commonly used in wear related applications in harsh tribological environments. However, the coarse carbide structure of the cast alloy results in higher brittleness and lower toughness. Hence this research was conducted to comprehend if carbide refinement, caused by changing the processing route to HIPing, could improve the tribomechanical performance of this alloy. Microstructural and tribomechanical evaluations, which involved hardness, impact toughness, abrasive wear, sliding wear, and contact fatigue performance tests, indicated that despite the similar abrasive and sliding wear resistance of both alloys, the HIPed alloy exhibited an improved contact fatigue and impact toughness performance in comparison to the cast counterpart. This difference in behavior is discussed in terms of the structure-property relationships. Results of this research indicated that the HIPing process could provide additional impact and fatigue resistance to this alloy without compromising the hardness and the abrasive/sliding wear resistance, which makes the HIPed alloy suitable for relatively higher stress applications. Results are also compared with a previously reported investigation of the Stellite 20 alloy, which had a much higher carbide content in comparison to the Stellite 6 alloy, caused by the variation in the content of alloying elements. These results indicated that the fatigue resistance did not follow the expected trend of the improvement in impact toughness. In terms of the design process, the combination of hardness, toughness, and carbide content show a complex interdependency, where a 40% reduction in the average hardness and 60% reduction in carbide content had a more dominating effect on the contact fatigue resistance when compared with an order of magnitude improvement in the impact toughness of the HIPed Stellite 6 alloy.