Non-typhoidal Salmonella (NTS) disease is usually a self-limiting infection presenting with digestive symptoms. However, disseminated presentation with involvement of secondary infectious sites is observed. We report diagnostic specificities and challenges related to the management of three patients with invasive NTS (iNTS) and secondary infectious locations. Among the seven patients (age range 46 - 83 years), four (two with extra-digestive infectious sites) had at least one immune debilitating condition. Two patients were incidentally discovered with iNTS and deceased after developing a septic shock despite antimicrobial treatment. Two individuals recovered under medical treatment without complications. Three other patients presented with secondary infectious sites. Case 1 suffered from urinary tract infection and dorsolumbar spondylodiscitis that responded well to antimicrobials and surgery. Abdominal prosthetic aortic aneurysm was diagnosed in case 2 and medical treatment only was applied. After four years of follow-up, he remains under antimicrobial treatment. Case 3 presented with conjoint thoracic aortic aneurysm and cutaneous abscesses managed with antimicrobials and surgery. Atherosclerosis and previous vascular intervention were the predisposing events for vascular involvement. iNTS is a serious disease carrying a high risk of mortality or secondary locations. Secondary locations can be managed by long duration antimicrobial therapy combined with surgery. Spine and aortitis are the most frequent secondary locations. Multi-drug resistant NTS represent an additional risk of mortality. Public health measures should be implemented to limit the spread of NTS to humans and the emergence of drug resistance.