Many　sensitizers　have　not　only　photodynamic　effects,　but　also　sonodynamic　effects.　Therefore,　the　combination　of　sonodynamic　therapy　(SDT)　and　photodynamic　therapy　(PDT)　using　sensitizers　for　sono-photodynamic　therapy　(SPDT)　provides　alternative　opportunities　for　clinical　cancer　therapy.　Although　significant　advances　have　been　made　in　synthesizing　new　sensitizers　for　SPDT,　few　of　them　are　successfully　applied　in　clinical　settings.　The　anti-tumor　effects　of　the　sensitizers　are　restricted　by　the　lack　of　tumor-targeting　specificity,　incapability　in　deep　intratumoral　delivery,　and　the　deteriorating　tumor　microenvironment.　The　application　of　nanotechnology-based　drug　delivery　systems　(NDDSs)　can　solve　the　above　shortcomings,　thereby　improving　the　SPDT　efficacy.　This　review　summarizes　various　sensitizers　as　sono/photosensitizers　that　can　be　further　used　in　SPDT,　and　describes　different　strategies　for　enhancing　tumor　treatment　by　NDDSs,　such　as　overcoming　biological　barriers,　improving　tumor-targeted　delivery　and　intratumoral　delivery,　providing　stimuli-responsive　controlled-release　characteristics,　stimulating　anti-tumor　immunity,　increasing　oxygen　supply,　employing　different　therapeutic　modalities,　and　combining　diagnosis　and　treatment.　The　challenges　and　prospects　for　further　development　of　intelligent　sensitizers　and　translational　NDDSs　for　SPDT　are　also　discussed.　(C)　2021　Chinese　Pharmaceutical　Association　and　Institute　of　Materia　Medica,　Chinese　Academy　of　Medical　Sciences.　Production　and　hosting　by　Elsevier　B.V.