ConspectusWhile traditional quantum chemical theories have long been central to research, they encounter limitations when applied to complex situations. Two of the most widely used quantum chemical approaches, Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT), perform well in cases with relatively weak electron correlation, such as the ground-state minima of closed-shell systems (Franck-Condon region). However, their applicability diminishes in more demanding scenarios. These limitations arise from the reliance of DFT on a single-determinantal framework and the inability of TDDFT to capture double and higher excited configurations in its response space.The recently developed Multi-Reference Spin-Flip Time-Dependent Density Functional Theory (MRSF-TDDFT) successfully overcomes these challenges, pushing the boundaries of DFT methods. MRSF-TDDFT is exceptionally versatile, making it suitable for various applications, including bond-breaking and bond-forming reactions, open-shell singlet systems such as diradicals, and a more accurate depiction of transition states. It also provides the correct topology for conical intersections (CoIns) and incorporates double excitations into the response space for a more precise description of excited states. With the help of its formal framework, core-hole relaxation for accurate X-ray absorption prediction can be also done readily. Notably, MRSF-TDDFT achieves an equal footing description of ground and excited states, with its dual-reference framework ensuring a balanced treatment of both dynamic and nondynamic electron correlations for high accuracy.In predictive tasks, such as calculating adiabatic singlet-triplet gaps, MRSF-TDDFT achieves accuracy comparable to that of far more computationally expensive coupled-cluster methods. The missing doubly excited state of H2 observed in TDDFT is accurately captured by MRSF-TDDFT, which also reproduces the correct asymptotic bond-breaking potential energy surface. Furthermore, the CoIns of butadiene, missed by both TDDFT and Complete-Active Space Self-Consistent Field (CASSCF) methods, are successfully recovered by MRSF-TDDFT, achieving results consistent with high-level theories, an important aspect for successful study of photochemical processes. Additionally, the common issue of CASSCF overestimating bright states (ionic states) due to the missing dynamic correlation is effectively resolved by MRSF-TDDFT.Despite its numerous advancements, MRSF-TDDFT retains the computational efficiency of conventional TDDFT, making it a practical tool for routine calculations. In addition, it has been demonstrated that the prediction accuracy of MRSF-TDDFT can be further enhanced through the development of tailor-made exchange-correlation functionals, paving the way for the creation of new, specialized functionals. Consequently, with its remarkable versatility, high accuracy, and computational practicality, this innovative method significantly expands scientists' ability to explore complex molecular behaviors and design advanced materials, including applications in photobiology, organic LEDs, photovoltaics, and spintronics, to name a few.