Obesity has become a global public health challenge, with its pathogenesis involving energy imbalance and multidimensional disorders in the neuro⁃immune⁃flora⁃heredity. Traditional weight loss interventions such as lifestyle modifications, pharmacotherapy, and surgical therapy still face bottle⁃neck in long⁃term efficacy, safety, and accessibility. This paper integrates evidence⁃based evidence from the past decade to elucidate the critical roles of the hypothalamic⁃limbic circuit, epigenetics, and flora metabolites in energy regulation. It summarizes the efficacy and limitations of conventional weight loss approaches, with a focus on the effects of multidimensional intervention strategies, including lifestyle modifications combined with non⁃traditional dietary management, pharmacotherapy combined with lifestyle modifications, bariatric metabolic surgery combined with medication, psychological and behavioral interventions, and Traditional Chinese Medicine or artificial intelligence⁃assisted lifestyle modifications. Additionally, it explores the application prospects of novel strategies such as hypothalamic neuronal regulation, gene therapy, and gut microbiota modulation, offering new insights for obesity management.

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