Background/objectives: The current systematic review considered research published within the 10 years preceding June 2019, dealing with the topic of obesity and pain. Within the context of the complex biological and behavioral interrelationships among these phenomena, we sought to identify gaps in the literature and to highlight key targets for future transdisciplinary research. The overarching inclusion criteria were that the included studies could directly contribute to our understanding of these complex phenomena. Methods: We searched PubMed/Medline/Cochrane databases dating back 10 years, using the primary search terms “obesity” and “pain,” and for a secondary search we used the search terms “pain” and “diet quality.” Results: Included studies (n = 70) are primarily human; however, some animal studies were included to enhance understanding of related basic biological phenomena and/or where human data were absent or significantly limited. Conclusions: Our overall conclusions highlight (1) the mechanisms of obesity-related pain (i.e., mechanical, behavioral, and physiological) and potential biological and behavioral contributors (e.g., gender, distribution of body fat, and dietary factors), (2) the requirement for accurate and reliable objective measurement, (3) the need to integrate biological and behavioral contributors into comprehensive, well-controlled prospective study designs.