Development of a photosensitizing system that can reversibly control the generation of singlet oxygen (1O2) is of great interest for photodynamic therapy (PDT). Recently several photosensitizer–photochromic‐switch dyads were reported as a potential means of the 1O2 control in PDT. However, the delivery of such a homogeneous molecular dyad as designed (e.g., optimal molar ratio) is extremely challenging in living systems. Herein we show a Zr‐MOF nanoplatform, demonstrating energy transfer‐based 1O2 controlled PDT. Our strategy allows for tuning the ratios between photosensitizer and the switch molecule, enabling maximum control of 1O2 generation. Meanwhile, the MOF provides proximal placement of the functional entities for efficient intermolecular energy transfer. As a result, the MOF nanoparticle formulation showed enhanced PDT efficacy with superior 1O2 control compared to that of homogeneous molecular analogues. A switch inside: In situ incorporation of a photosensitizing system into MOF nanoparticles to control 1O2 generation is possible using a tunable ratio of a photochromic switch. The MOF formulation allows enhanced in vitro photodynamic therapy (PDT) efficacy with a superior control of 1O2 production compared to a simple mixture of the dyad.