Recently surface-enhanced Raman scattering (SERS) imaging guided theranostic nanoplatforms have attracted considerable attention. Herein, we developed novel yolk-shell gold nanorod@void@mesoporous titania nanoparticles (AuNR@void@mTiO₂ NPs) for simultaneous SERS imaging and chemo-photothermal therapy. Our work showed three highlighted features: first, we proposed a facile and versatile "up to down" SERS labeling strategy for the drug delivery system, in which "empty carriers" were pre-synthesized, followed by co-loading of Raman reporters on AuNR and anti-cancer drug doxorubicin (DOX) in mTiO₂ in sequence. The acquired SERS signal was strong enough for tracking NPs at both living cells and mice levels. Second, we selected mTiO₂ as a novel drug loading material instead of the widely used mesoporous silica (mSiO₂). The mTiO₂ shared satisfactory drug loading and release behavior as mSiO₂ but it was chemically inert. This property not only provided a facile way to form a yolk-shell structure but also rendered it with superior structural stability in a biological system. Third, the near infrared (NIR) light absorbing property of the AuNR SERS substrate was also explored for drug release regulation and photothermal treatment. Significantly greater MCF-7 cell killing was observed when treated together with DOX-loaded NPs and NIR laser irradiation, attributable to the synergistic chemo-thermal therapeutic effect. Our results indicated the established SERS labeled yolk-shell NP as a promising theranostic platform and suggested its potential in vivo applications.