A particular challenge in the design of organic photosensitizers (PSs) with donor–acceptor (D‐A) structures is that it is based on trial and error rather than specific rules. Now these challenges are addressed by proposing two efficient strategies to enhance the photosensitization efficiency: polymerization‐facilitated photosensitization and the D‐A even–odd effect. Conjugated polymers have been found to exhibit a higher 1O2 generation efficiency than their small molecular counterparts. Furthermore, PSs with A‐D‐A structures show enhanced photosensitization efficiency over those with D‐A‐D structures. Theoretical calculations suggest an enhanced intersystem crossing (ISC) efficiency by these strategies. Both in vitro and in vivo experiments demonstrate that the resulting materials can be used as photosensitizers in image‐guided photodynamic anticancer therapy. These guidelines are applicable to other polymers and small molecules to lead to the development of new PSs. Conjugated polymers have a higher 1O2 generation efficiency than their small molecular counterparts. Photosensitizers with A‐D‐A structures are better than D‐A‐D structures. Both in vitro and in vivo experiments show that the resulting materials can be used as photosensitizers in image‐guided photodynamic anticancer therapy. D=donor, A=acceptor.