Based on a review of relevant literature published between 2004 and 2025 in PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure, together with current guidelines, expert consensus statements, and representative clinical studies, this article proposes a four-domain integrated framework for oral and maxillofacial multispace infection (OMSI) centered on the physiology-inflammation axis. The framework is intended to support risk stratification and pathway-oriented management of severe OMSI by integrating evidence across four domains: Physiological decompensation, infection extent and anatomical involvement, inflammatory response, and host reserve. Risk assessment of severe OMSI should not depend on any single indicator. The proposed physiology-inflammation axis-based framework applies weighted integration of clinical information, in which physiological decompensation and infection extent with anatomical involvement directly determine the urgency of early intervention, whereas inflammatory response and host reserve are used to assess infection activity, treatment response, and the patient's tolerance of infection, anesthesia, surgery, and other interventions. Pathway-oriented management is organized around key time windows: Airway assessment and initial resuscitation at 0 h<t≤1 h, incision and drainage with source control at 1 h<t≤6 h, intensified multisystem monitoring at 6 h<t≤24 h, the first systematic reassessment at 24 h<t≤48 h, and de-escalation, rehabilitation, and follow-up at t>48 h according to the patient's clinical condition. By incorporating risk-factor identification, bedside assessment, risk stratification, and multidisciplinary collaboration into a unified decision-making pathway, the framework may facilitate the early identification of high-risk patients and the organization of structured clinical management. At present, the framework remains exploratory, and the weighting of individual indicators, threshold settings, and boundaries of clinical applicability require further validation and refinement through multicenter prospective studies.