Background: Urothelial Carcinoma (UC) of urinary bladder is the most predominant histologic pattern of bladder cancer (BC). Studying the prognostic aspects of UC through spotting the light on Yes-associated protein 1 (YAP1) together with TAMs may help to know their role in prognosis of UC. Aim: Our study targets reviewing the immunohistochemical reactivity of YAP1 and TAMs marker CD68 in UC. Also, to evaluate the relation between YAP1 and CD68 with the available clinicopathologic parameters in UC and with each other. Material and methods: Eighty-two paraffin blocks of UC collected retrospectively and included 62 trans-urethral resection of bladder tumor (TURBT) specimens and 20 specimens from radical cystectomies. All were stained with H&E, YAP1, and CD68. Results: YAP1 expression was related significantly to large sized tumors, histopathologic subtypes of UC (conventional UC versus plasmacytoid type), high tumor grade, advanced pT and N stage, and perineural invasion (PNI). CD68+ TAMs mean count was significantly related to large tumor size, the histopathologic types of UC (papillary non-invasive versus invasive), histopathologic subtypes of UC (conventional UC versus UC with squamous differentiation and plasmacytoid type), tumor grade, advanced pT stage, and PNI. Conclusion: High YAP1 expression and CD68+ TAMs high mean count was significantly related with adverse pathological factors namely, large sized tumors, tumors of high grade, and advanced pT stage. Their expression in UC could be used in identifying patients at increased risk of tumor invasion and progression.