On October 11, 2021, at 1214 Pacific daylight time, a Cessna 340A, N7022G, was destroyed when it was involved in an accident near Santee, California. The pilot and one person on the ground were fatally injured, and 2 people on the ground sustained serious injuries. The airplane was operated as a Title 14 Code of Federal Regulations Part 91 personal flight. The flight departed from Yuma International Airport (NYL), Yuma, AZ at 1121 mountain daylight time and was destined for Montgomery-Gibbs Executive Airport (MYF), San Diego, California. Review of Federal Aviation Administration Southern California Terminal Radar Approach Control (TRACON) facilities and recorded Automatic Dependent Surveillance-Broadcast (ADS-B) data revealed that at 1203:58, the controller broadcasted a weather update for MYF and reported the visibility was 10 miles, ceiling 1,700 ft broken, overcast skies at 2,800 ft, and runway 23 was in use. At 1209:20, the controller issued instructions to the pilot to turn right to a 259° heading to join final, to which the pilot acknowledged while at an altitude of 3,900 ft mean sea level (msl). About 28 seconds later, the pilot queried the controller and asked if he was cleared for the ILS Runway 28R approach, with no response from the controller. At 1210:04, the controller told the pilot that he was 4 miles from PENNY intersection and instructed him to descend to 2,800 ft until established on the localizer, and cleared him for the ILS 28R approach, circle to land runway 23. The pilot partially read back the clearance, followed by the controller restating the approach clearance. The pilot acknowledged the clearance a second time. At this time, the ADS-B data showed the airplane on a westerly heading, at an altitude of 3,900 ft msl. Immediately following a traffic alert at 1211:19, the controller queried the pilot and stated that it looked like the airplane was drifting right of course and asked him if he was correcting. The pilot responded and stated “correcting, 22G.” About 9 seconds later, the pilot said [unintelligible], VFR 23, to which the controller told the pilot he was not tracking the localizer and canceled the approach clearance. The controller followed by issuing instructions to climb and maintain 3,000 ft, followed by the issuance of a low altitude alert, and stated that the minimum vectoring altitude in the area was 2,800 ft. The pilot acknowledged the controller’s instructions. At that time, ADS-B data showed the airplane on a northwesterly heading, at an altitude of 2,400 ft msl. At 1212:12, the controller instructed the pilot to climb and maintain 3,800, to which the pilot responded “3,800, 22G.” ADS-B data showed that the airplane was at 3,550 ft msl. About 9 seconds later, the controller issued the pilot instructions to turn right to 090° for vectors to final, to which the pilot responded “090 22G.” At 1212:54, the controller instructed the pilot to turn right to 090° and climb immediately and maintain 4,000 ft. The pilot replied shortly after and acknowledged the controller’s instructions. About 3 seconds after the pilot’s response, the controller told the pilot that it looked like he was descending and that he needed to make sure he was climbing, followed by an acknowledgment from the pilot. At 1213:35, the controller queried the pilot about his altitude, which the pilot responded 2,500 ft. The controller subsequently issued a low altitude alert and advised the pilot to expedite the climb to 5,000 ft. No further communication was received from the pilot despite multiple queries from the controller. ADS-B data showed that the airplane continued a right descending turn until the last recorded target, located about 1,333 ft northwest of the accident site at an altitude of 1,250 ft msl. Figure 1 provides an overview of the ADS-B flight track, select ATC communications, and the location of the destination and surrounding area airports. Examination of the accident site revealed that the airplane impacted a residential street on a heading of about 113° magnetic heading. The debris path, which consisted of various airplane, vehicle, and residential structure debris was about 475 ft long and 400 ft wide, oriented on a heading of about 132°. Numerous residential structures exhibited impact related damage and or fire damage. All major structural components of the airplane were located throughout the debris path.