Misalignment is among the most common causes of vibrations in rotary machinery. Modern machinery is complicated and installing a sensor might be tricky at times. As a result, noncontact type sensors are critical in such situations. The present study investigates the influence of combinations between speed, load, and fault severity upon system vibration by employing acoustic sensor. Although acoustic sensor is used in angular fault diagnosis, however, this is the first attempt to combine the noncontact type of sensor and response surface methodology (RSM) to study the influence of misalignment upon system vibration and the factors that induce system vibrations in a misaligned rotor system. To investigate the effect of these interactions on system performance, RSM with root-mean-square (RMS) as a response factor is used. Design of experiments is used to prepare experiments, while analysis of variance (ANOVA) is used to analyze the results. Speed has a significant impact on RMS value in both parallel and angular types of misalignments and it severely affects the system's performance. According to the RSM findings, a change in load influences vibration amplitude. With increasing defect severity, the change in RMS value was not particularly significant. The outcome of RSM using acoustic sensor was found well aligned with the conclusion drawn using RSM study with vibrational sensor.