The treatment mode of hepatocellular carcinoma (HCC) is gradually evolving towards individualized sequential local combined with systemic therapy. TACE combined with microwave ablation (MWA) is an important local combined therapy for HCC, and its efficacy is affected by both tumor volume and sequential time window. In this article, clinical evidence and mechanism of TACE-MWA in different stratifications of tumor volume (≤3 cm, 3-5 cm, ≥5 cm) and different sequential time windows (synchronous/ultrashort, 1-4 weeks, long interval/sequential). TACE can reduce the ‘heat sink effect’ by reducing the blood supply of tumors, while lipiodol deposition can improve the development and thermal efficiency of MWA. Both of them can induce immunogenic cell death and activate systemic anti-tumor immunity. For medium-sized HCC (3-5 cm), MWA within 1-4 weeks after TACE can significantly improve the complete remission rate and prolong the tumor progression time. For large/huge HCC (≥5 cm), multi-modal strategy of sequential tumor reduction or combined with targeted therapy/immunotherapy. Existing evidence is still mainly based upon retrospective research, with a significant degree of heterogeneity, including differences in TACE/MWA technology, inconsistent definition of endpoint, and different baselines of patients, which limit the universality of the conclusion. Individualized sequential strategy based on tumor volume and time window possesses definite pathophysiological evidence and clinical benefit trend. However, it is necessary to comprehensively weigh between‘the optimal window of hemodynamics’and‘the safe window of liver function’. Peripheral immune markers (such as NLR and NK cell dynamics) may provide potential evidence for time window optimization, whereas the causal effects remain to be verified by prospective study. Subsequently, multi-center stratified randomized trials should be carried out, with‘time window’as the core variable, and dynamic indexes of hemodynamics, immunity and liver function should be systematically collected. In addition, it is necessary to unify technical specifications and endpoint evaluation standards, aiming to establish an individualized treatment system based on‘tumor volume-time window-hemodynamics/immune dynamics’and promote the evolution of combined therapy for HCC in the precise and evidence-based direction.