Background/Objectives: Diabetic foot syndrome (DFS) is a serious complication of diabetes that poses a high risk of morbidity/mortality. The management of these patients requires a multidisciplinary team approach, as these patients are “complex” and “fragile”. Despite this, the rate of re-amputation remains high. This study aims to evaluate the degree of multidimensional complexity in patients with DFS using specific tools and to determine if it is an additional risk factor for amputation. Methods: The study was conducted on a cohort of 115 patients referred to a Tertiary Center of University Hospital of Modena from January to December 2021. The study used 12 variables to assess patients, including age, sex, caregiver presence, BARTHEL INDEX, LAWTON-BRODY SCALE, Mini Mental State Examination, Cumulative Illness Rating Scale (CIRS), SINBAD system, Malnutrition Universal Screening Tool and Italian National Association of Social Workers Tool. All patients were taken care of by the Multidisciplinary Team in order to standardize care according to the updated guidelines. Patients were classified based on amputation and revascularization status. Statistical analyses were performed using R software version 4.1.1. Results: The analysis showed that a greater clinical complexity and more severe ulcer had a greater risk of amputation (respectively OR 3.13, p 0.035 and OR 1.53, p 0.015). The study confirms the predictive value of tools such as CIRS and SINBAD in amputation risk stratification for patients with DFS. Conclusions: Although limitations, due to a small sample size, the use of multidisciplinary approach and multidimensional evaluation tools can identify “unconventional” risk factors that, if modified, could delay and/or reduce the risk of amputation. Further studies are needed to investigate the role of caregiving in the prevention of amputation in patients with DFS.