The onset and progression of cardiovascular-kidney-metabolic (CKM) syndrome involve the interaction among metabolic abnormality, chronic kidney disease, and cardiovascular disease. Current clinical management of this condition has limitations, such as fragmented diagnosis and treatment and insufficient control of target organ damage. Traditional Chinese medicine emphasizes holistic syndrome differentiation and individualized intervention. It has unique advantages in preventing and treating comorbidities. This paper is based on the core concepts of Huangdi Neijing, combined with the theory of the membrane system. It clarifies the internal correlation among the spleen and stomach, the membrane system and the vessels and collaterals in terms of structure, function, and pathological process. It also analyzes the pathogenesis evolution rule of CKM syndrome from stage 0 to 4. CKM syndrome starts with the dysfunction of transportation and transformation of the spleen and stomach, and stagnation of the membrane system at stages 0 and 1. It then progresses to the retention of turbid pathogens in the membrane system and qi flow blockage in vessels and collaterals at stage 2. The disease further develops into intermingled phlegm and blood stasis and concurrent disorder of the membrane system and collaterals at stage 3. It eventually leads to the decline of primordial qi and complete exhaustion of the membrane system and collaterals at stage 4. Clinically, a staged treatment strategy has been proposed based on the core therapeutic principles of "eliminating pathogenic factors, harmonizing the body, and providing protection." The strategy includes dredging and regulating the sanjiao and diffusing and smoothing the membrane system at the early stage. It adopts clearing and resolving turbid pathogen and smoothing qi flow in collaterals at the middle stage. Resolving phlegm, eliminating blood stasis, unblocking collaterals, and dissipating masses are applied at the late stage. At the end stage, the core strategy is to strengthen healthy qi, consolidate the root, and combine unblocking and tonifying therapies. This paper aims to provide a reference for the clinical intervention of CKM syndrome.