Peritoneal metastasis is the result of direct shedding of tumor cells from ovarian, colorectal, and other cancers that lead to studding and growth on the peritoneal surfaces and abdominal organs. Standard chemotherapy and surgery can transiently improve symptoms, but long-term disease control and survival extension remain rare due to residual disease and treatment resistance. In the past 40 years, tremendous progress in photoimmunotherapy (PIT) has been made to treat metastasis. However, many are lost in translation due to heterogeneity in photosensitizer drug uptake and treatment response. Therefore, it is critical to develop targeted therapies with a multimodal approach that integrates well with current standards of care strategies and overcomes heterogeneous delivery and treatment responses. Our novel targeted photo-activable mult-agent liposomal platform combined with fluorescence-guided PIT has demonstrated its capabilities to overcome these challenges in our prior work and we further demonstrate its efficacy by studying (1) tumor nodule penetration depth, (2) tissue optical property changes pre and post multi-dose PIT, and (3) enhanced long term therapeutic efficacy compared to monotherapy treated groups in a mouse peritoneal carcinomatosis model.