Background/Objectives: Despite the increasing number of available medications, a significant proportion of IBD patients fail to achieve the current therapeutic targets. Uncontrolled IBD has a significant impact on patients’ quality of life and on overall costs for the healthcare system. Given the complex pathophysiology of IBD, Combined Advanced Targeted Therapy (CATT), involving the combination of biologics/small molecules, appears to have biological plausibility and is gaining increasing interest. The aim of this narrative review is to provide the current evidence regarding CATT in IBD and propose future developments in this field. Methods: Relevant literature evidence was searched with pertinent MeSH terms in the most important database. Results: Available evidence of CATT in IBD provides encouraging results in terms of efficacy and effectiveness, with an acceptable safety profile. CATT may represent a therapeutic solution for patients with “difficult-to-treat” IBD or with concomitant immune-mediated inflammatory diseases. However, current data are restricted by an overall low level of evidence and by the short follow-up. Conclusions: There are no data concluding the superiority of one combination therapy over another. Various therapeutic schemes could be applied in the near future. Further studies are needed to provide recommendations and integrate this therapeutic strategy into everyday clinical practice.

Background/Objectives: Upper gastrointestinal Crohn’s disease (UGI-CD) is inconsistently defined and often underrecognized, obscuring epidemiology, complicating diagnosis, and delaying tailored care. The absence of a unified, operational definition with segment-specific criteria hinders reproducibility and comparability across studies. Methods: We performed a narrative synthesis of adult and pediatric studies and major guidelines, examining definitions, prevalence, diagnosis, and management. Where possible, findings were mapped to upper GI segments (esophagus, stomach, duodenum, proximal small bowel). Results: Definitions of UGI-CD are heterogeneous. Prevalence varies widely and rises with systematic foregut assessment; isolated upper GI disease without ileocolonic involvement is rare. Diagnosis relies on esophagogastroduodenoscopy with biopsies, complemented by cross-sectional imaging and enteroscopy. Management should extend beyond standard ileocolonoscopy, with segment-tailored monitoring. Anti-TNF agents show the most consistent efficacy in esophagogastroduodenal disease, whereas benefits are attenuated in proximal small bowel involvement. For stricturing disease, endoscopic balloon dilation is suitable for short, non-penetrating strictures but often requires repetition; surgery is preferred for complex anatomy or failed dilation. A short summary of the article’s main findings is provided. Conclusions: UGI-CD remains poorly standardized across definition, epidemiology, and management. We propose a pragmatic diagnostic and monitoring pathway and highlight priorities for research: segment-based reporting, inclusion of upper GI-only cohorts, and validation of treatment targets aligned with treat-to-target care—steps essential to improve early recognition and patient outcomes.