Photocatalysis process is a promising technology for environmental remediation. In the continuous search of new heterogeneous photocatalysts, metal-organic frameworks (MOFs) have recently emerged as a new type of photoactive materials for water remediation. Particularly, titanium-based MOFs (Ti-MOFs) are considered one of the most appealing subclass of MOFs due to their promising optoelectronic and photocatalytic properties, high chemical stability, and unique structural features. However, considering the limited information of the reported studies, it is a hard task to determine if real-world water treatment is attainable using Ti-MOF photocatalysts. In this paper, via a screening with several Ti-MOFs, we originally selected and described the potential of a Ti-MOF in the photodegradation of a mixture of relevant Emerging Organic Contaminants (EOCs) in real water. Initially, two challenging drugs (i.e., the β-blocker atenolol (At) and the veterinary antibiotic sulfamethazine (SMT)) and four water stable and photoactive Ti-MOF structures have been rationally selected. From this initial screening, the mesoporous Ti-trimesate MIL-100(Ti) was chosen as the most promising photocatalyst, with higher At or SMT individual photodegradation (100% of At and SMT photodegradation in 2 and 4 h, respectively). Importantly, the safety of the formed by-products from the At and SMT photodegradation was confirmed. Finally, the At and SMT photodegradation capacity of MIL-100(Ti) was confirmed under realistic conditions, by using a mixture of contaminants in tap drinking water (100% of At and SMT photodegradation in 4 h), proven in addition its potential recyclability, which reinforces the potential of MIL-100(Ti) in water remediation.