Zygomatic implants have emerged as a promising surgical technique to rehabilitate severe atrophic maxilla and maxillectomy. However, this implant design lacks an appropriate standard test protocol. This study aimed to simulate and evaluate zygomatic implants under compressive and lateral loads using finite element analysis, following the current ISO parameters for dental implants, employing different cylindrical holders. These holders simulate the bone configuration of clinical scenarios of the zygoma anatomic-guided approach (ZAGA) and maxillectomy rehabilitation with zygomatic implants. Six three-dimensional models were generated and subjected to a 150 N compressive load at a 40° angle. In the next step, a simultaneous 50 N lateral load was applied. Von Mises stress data and contour plots were collected and analyzed. Von Mises peak stresses increased by more than 100% when a lateral load was applied. Data demonstrated the influence of the setup support and lateral load on the implant components’ peak stress values.