Organic π-systems with strong absorption in the near-infrared (NIR) region are promising candidates for photothermal therapy (PTT) and photodynamic therapy (PDT). However, the synthesis of NIR π-systems involves several steps and many of them display poor photothermal conversion efficiency (PTCE). Here we present the synthesis of a tetraimide-based donor-acceptor NIR π-system, 2EHex-B having absorbance in the range of 350–900 nm. Importantly, 2EHex-B is synthesized in two steps with a 70 % high yield. Moreover, 2EHex-B shows excellent PTCE up to 50 % and good biocompatibility when encapsulated in liposomes. The liposome coated 2EHex-B, (L-2EHex-B) showed good thermal stability and efficiently kills cancer cells via PTT. Additionally, L-2EHex-B shows good reactive singlet oxygen generation ability when irradiated with a 750 nm laser. 3D cell culture model - multicellular spheroids test was performed to evaluate the efficiency of PTT. The spheroids treated with L-2EHex-B after NIR light irradiation showed increased cell death from the core of the tumor toward the periphery. The easy access to 2EHex-B makes it a potential candidate for minimally invasive cancer treatment. © 2023 Wiley-VCH GmbH.