Asphalt mixes often have many ingredients that can interact with each other. When put into service, where there are multiple environmental effects, there are many interactions that need mixture testing. This paper’s objective was to evaluate laboratory conditioning protocols coupled with subsequent property measurements for their ability to detect damage of asphalt mixtures in the southeastern U.S. climate (or similar climates). The investigation’s focus is the property measurements themselves, and in particular how a given test can simultaneously assess multiple types of damage (i.e. oxidation, moisture damage, and freeze-thaw damage). While in service, mixtures can be damaged in multiple manners so laboratory conditioning protocols that expose specimens to multiple types of damage are needed as are test(s) that can detect these damages in a manner that can help assess performance during service. Four plant produced mixtures with all virgin ingredients were evaluated at intermediate temperatures with mixture and binder tests. The mixtures were well suited for such a comparison because they consisted of all virgin binder. Indirect tensile (IDT) strength did not relate to Cantabro Mass Loss (CML) or binder test results, which was concerning. Even more concerning was IDT’s inability to respond to laboratory conditioning protocols that considered multiple environmental effects (i.e., oxidation, moisture, and freeze-thaw). CML results related to binder properties and were able to reasonably detect multiple types of environmental effects. As such, Cantabro testing is recommended over tensile strength for intermediate temperature mixture property assessments related to non-load associated environmental effects.