Sorafenib,　a　molecular　targeted　multi-kinase　inhibitor,　has　received　considerable　interests　in　recent　years　due　to　its　significant　profiles　of　efficacy　in　cancer　therapy.　However,　poor　pharmacokinetic　properties　such　as　limited　water　solubility,　rapid　elimination　and　metabolism　lead　to　low　bioavailability,　restricting　its　further　clinical　application.　Over　the　past　decade,　with　substantial　progress　achieved　in　the　development　of　nanotechnology,　various　types　of　smart　sorafenib　nanoformulations　have　been　developed　to　improve　the　targetability　as　well　as　the　bioavailability　of　sorafenib.　In　this　review,　we　summarize　various　aspects　from　the　preparation　and　characterization　to　the　evaluation　of　antitumor　efficacy　of　numerous　stimuli-responsive　sorafenib　nanodelivery　systems,　particularly　with　emphasis　on　their　mechanism　of　drug　release　and　tumor　microenvironment　response.　In　addition,　this　review　makes　great　effort　to　summarize　the　nanosystem-based　combination　therapy　of　sorafenib　with　other　antitumor　agents,　which　can　provide　detailed　information　for　further　synergistic　cancer　therapy.　In　the　final　section　of　this　review,　we　also　provide　a　detailed　discussion　of　future　challenges　and　prospects　of　designing　and　developing　ideal　sorafenib　nanoformulations　for　clinical　cancer　therapy.　(C)　2020　Shenyang　Pharmaceutical　University.　Published　by　Elsevier　B.V.