• Arm 1: Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit.

• Arm 2: Have a histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC (Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemoradiation, or Stage IV NSCLC, AJCC Staging Manual, version 8).

• Arm 2: Confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy

• Arm 2: Has tumor tissue that demonstrates PD-L1 TPS ≥ 50% as determined by PD-L1 IHC 22C3 pharmDx assay by local laboratory

• If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (100 days for sacituzumab tirumotecan and 90 days for carboplatin \[no restriction for pembrolizumab\]) AND agrees to refrain from donating sperm AND is either abstinent and agrees to remain abstinent or uses highly effective contraception

• For females (assigned at birth), is not pregnant or breastfeeding and ≥1 of the following applies: is not a participant of childbearing potential (POCBP) OR is a POCBP and uses highly effective contraception

• Arm 1: Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline

• Measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology

• Archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated has been provided

• Have a life expectancy of at least 3 months

• Have an ECOG performance status of 0 or 1 within 3 days before the start of study intervention