The spleen plays a crucial role in filtering aging blood cells and defending against encapsulated microorganisms. While not essential for survival, splenic dysfunction can lead to severe complications, including organ failure, infection, and death. This case study examines a rare presentation of drug-induced splenic septic thrombophlebitis secondary to pancreatitis caused by an adverse reaction to ceftriaxone. While pancreatitis is a known, common cause of splenic infarction and sepsis, there have only been two reported cases of ceftriaxone-induced pancreatitis in the past decade. This case follows a 26-year-old female with a history of congenital truncus arteriosus, who initially presented with Streptococcus mitis bacteremia secondary to prosthetic heart-valve endocarditis and was treated with ceftriaxone. On day 21 of ceftriaxone treatment, the patient returned with septic splenic thrombophlebitis secondary to acute pancreatitis. The patient clinically improved and showed a decrease in inflammatory markers following the discontinuation of ceftriaxone. These findings aim to present a rare case of ceftriaxone-induced pancreatitis. The successful diagnosis and conservative management of our patient underscore the critical importance of interdisciplinary collaboration in the management of complex cases, ultimately avoiding unnecessary surgical interventions.