Modern vehicles are prime examples of cyber-physical systems that rely on multiple domains, including mechanics, electronics, and software. Due to high customizability and software changes, introduced by bug fixes or functional upgrades, vehicle instances vary in space (variants) and time (versions). This results in an extremely large number of possible variants and versions; thus, testing all of them to ensure functional safety is practically infeasible. Moreover, components of all domains interact with each other; thus, solely focusing on single domains while testing multi-domain cyber-physical systems is insufficient. In this paper, we identify challenges that arise from multi-domain dependencies when testing multi-domain cyber-physical systems and propose a change-aware testing process as a basis for future work. The process is structured in three steps: (1) selection of variants and versions to reduce overall testing effort by focusing on testing the variants and versions affected by a change; (2) selection and prioritization of test cases ”relevant” for addressing changes in the system under test and its application domain; (3) adaption of the test environment considering the change-aware test case- and system under test selection.